# NM_001385682.1(MAP4):c.1882G>A (p.Val628Ile)

https://sugi.bio/variant/map4-p-val628ile

## Summary

**MAP4 p.Val628Ile (c.1882G>A)** is classified **Benign** in MAP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-25). AlphaMissense: likely benign (0.0793); Common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MAP4-related disorder.

**At a glance:** Benign · review: No assertion criteria · rsID rs1137524 · 1 submitter · 1 linked condition · AlphaMissense likely benign · common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele

## For patients & families {#patients}

This is a change in the MAP4 gene that is classified as benign — not considered disease-causing, submitted by 1 submitter, and is linked to MAP4-related disorder.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [MAP4](https://sugi.bio/atlas/gene/MAP4/) |
| Protein change (HGVS p.) | p.Val628Ile |
| Coding change (HGVS c.) | c.1882G>A |
| MANE Select transcript | [NM_001385682](https://www.ncbi.nlm.nih.gov/nuccore/NM_001385682) |
| dbSNP | [rs1137524](https://www.ncbi.nlm.nih.gov/snp/rs1137524/) |
| Variant type | single nucleotide variant |
| Location | chr3:47914934-47914934 (GRCh38) |
| ClinVar | [VCV3060070](https://www.ncbi.nlm.nih.gov/clinvar/variation/3060070/) |

**All HGVS expressions:** `NC_000003.11:g.47956424C>T`, `NC_000003.12:g.47914934C>T`, `NG_052840.1:g.179346G>A`, `NM_001134364.2:c.1882G>A`, `NM_001384675.1:c.1759G>A`, `NM_001384676.1:c.1882G>A`, `NM_001384677.1:c.1882G>A`, `NM_001384678.1:c.1918G>A`, `NM_001384679.1:c.1882G>A`, `NM_001384680.1:c.1576G>A`, `NM_001384681.1:c.1759G>A`, `NM_001384707.1:c.1759G>A`, `NM_001384729.1:c.1882G>A`, `NM_001384730.1:c.1813G>A`, `NM_001384731.1:c.1933G>A`, `NM_001384733.1:c.1882G>A`, `NM_001384734.1:c.1882G>A`, `NM_001384735.1:c.1882G>A`, `NM_001384736.1:c.1933G>A`, `NM_001384737.1:c.1882G>A`, `NM_001384738.1:c.1918G>A`, `NM_001384744.1:c.1810G>A`, `NM_001384745.1:c.1918G>A`, `NM_001384746.1:c.1690G>A`, `NM_001384748.1:c.1918G>A`, `NM_001384751.1:c.1882G>A`, `NM_001384752.1:c.1882G>A`, `NM_001384753.1:c.1690G>A`, `NM_001384754.1:c.1882G>A`, `NM_001384755.1:c.1759G>A`, `NM_001384756.1:c.1882G>A`, `NM_001384757.1:c.1690G>A`, `NM_001384758.1:c.1768G>A`, `NM_001384759.1:c.1759G>A`, `NM_001384760.1:c.1759G>A`, `NM_001384761.1:c.1882G>A`, `NM_001384762.1:c.658G>A`, `NM_001384774.1:c.1882G>A`, `NM_001384776.1:c.1768G>A`, `NM_001384777.1:c.1813G>A`, `NM_001384778.1:c.1249G>A`, `NM_001384779.1:c.1882G>A`, `NM_001384780.1:c.1813G>A`, `NM_001384781.1:c.1882G>A`, `NM_001384782.1:c.1813G>A`, `NM_001384783.1:c.1813G>A`, `NM_001384784.1:c.658G>A`, `NM_001384785.1:c.1882G>A`, `NM_001384786.1:c.1813G>A`, `NM_001384787.1:c.1813G>A`, `NM_001384788.1:c.1933G>A`, `NM_001384789.1:c.1810G>A`, `NM_001384790.1:c.1933G>A`, `NM_001384791.1:c.1810G>A`, `NM_001384792.1:c.1933G>A`, `NM_001384793.1:c.1810G>A`, `NM_001384794.1:c.1933G>A`, `NM_001384795.1:c.1969G>A`, `NM_001384796.1:c.1933G>A`, `NM_001384797.1:c.1810G>A`, `NM_001384798.1:c.1882G>A`, `NM_001384800.1:c.1882G>A`, `NM_001384802.1:c.529+6831G>A`, `NM_001384803.1:c.1645G>A`, `NM_001384804.1:c.1759G>A`, `NM_001384805.1:c.1759G>A`, `NM_001384806.1:c.1759G>A`, `NM_001384807.1:c.1645G>A`, `NM_001384808.1:c.529+6831G>A`, `NM_001384809.1:c.1882G>A`, `NM_001384810.1:c.1882G>A`, `NM_001384811.1:c.1813G>A`, `NM_001384812.1:c.529+6831G>A`, `NM_001384813.1:c.622-42G>A`, `NM_001384814.1:c.1882G>A`, `NM_001384815.1:c.529+6831G>A`, `NM_001384816.1:c.1813G>A`, `NM_001384817.1:c.460+6831G>A`, `NM_001384819.1:c.1882G>A`, `NM_001384820.1:c.1882G>A`, `NM_001384824.1:c.1882G>A`, `NM_001384825.1:c.1768G>A`, `NM_001384826.1:c.1759G>A`, `NM_001384827.1:c.1882G>A`, `NM_001384828.1:c.1813G>A`, `NM_001384831.1:c.1882G>A`, `NM_001384832.1:c.1768G>A`, `NM_001384834.1:c.1792G>A`, `NM_001384835.1:c.529+6831G>A`, `NM_001384836.1:c.1759G>A`, `NM_001384837.1:c.1759G>A`, `NM_001384838.1:c.1882G>A`, `NM_001384839.1:c.1561G>A`, `NM_001384840.1:c.1882G>A`, `NM_001384841.1:c.1768G>A`, `NM_001384842.1:c.1645G>A`, `NM_001384843.1:c.1645G>A`, `NM_001384844.1:c.1882G>A`, `NM_001384845.1:c.1561G>A`, `NM_001384846.1:c.1882G>A`, `NM_001384847.1:c.1882G>A`, `NM_001384848.1:c.1882G>A`, `NM_001384849.1:c.1843G>A`, `NM_001384850.1:c.1759G>A`, `NM_001384851.1:c.1768G>A`, `NM_001384853.1:c.1759G>A`, `NM_001384856.1:c.1249G>A`, `NM_001384857.1:c.1813G>A`, `NM_001384859.1:c.1804G>A`, `NM_001384861.1:c.1882G>A`, `NM_001384862.1:c.1438G>A`, `NM_001384863.1:c.1966G>A`, `NM_001384864.1:c.1690G>A`, `NM_001384866.1:c.1759G>A`, `NM_001384867.1:c.1561G>A`, `NM_001384868.1:c.1759G>A`, `NM_001384869.1:c.1813G>A`, `NM_001384870.1:c.1882G>A`, `NM_001384871.1:c.1882G>A`, `NM_001384872.1:c.1918G>A`, `NM_001384873.1:c.1804G>A`, `NM_001384874.1:c.1792G>A`, `NM_001384875.1:c.1918G>A`, `NM_001384876.1:c.1768G>A`, `NM_001384877.1:c.535G>A`, `NM_001384878.1:c.1876+1017G>A`, `NM_001384879.1:c.1882G>A`, `NM_001384892.1:c.1792G>A`, `NM_001384893.1:c.1759G>A`, `NM_001385664.1:c.1813G>A`, `NM_001385665.1:c.1882G>A`, `NM_001385675.1:c.1918G>A`, `NM_001385676.1:c.1690G>A`, `NM_001385677.1:c.1882G>A`, `NM_001385681.1:c.1933G>A`, `NM_001385682.1:c.1882G>A`, `NM_001385684.1:c.1882G>A`, `NM_001385685.1:c.1882G>A`, `NM_001385686.1:c.1933G>A`, `NM_001385687.1:c.1933G>A`, `NM_001385688.1:c.1933G>A`, `NM_001385689.1:c.1933G>A`, `NM_002375.5:c.1882G>A`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele.

- AlphaMissense **likely benign** (0.0793)
- REVEL 0.054 (moderately benign-leaning) — agrees with AlphaMissense
- SaProt LLR -7.243 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP -1.037, GERP -2.93 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 1.752**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- Regional missense constraint: **o/e 0.91** across the covering region of the MANE Select transcript (47,875,838–47,998,860), spanning 123,022 bp. Chi-square p 2.5e-05. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>A, Δ0.22 acceptor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **52.5%** (afr) · FAF95 52.1% · FAF99 51.9% · 39,286/74,842 in the highest group · 515,628/1,613,292 alleles overall — common (popmax 52.5%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 52.5% | 2 |
| Middle Eastern | 38.2% | 3 |
| Admixed American | 37.6% | 3 |
| Ashkenazi Jewish (not grpmax-eligible) | 37.4% | 3 |
| South Asian | 37.2% | 3 |
| Remaining individuals (not grpmax-eligible) | 33.6% | 3 |
| European (non-Finnish) | 30.5% | 3 |
| Amish (not grpmax-eligible) | 29.6% | 3 |
| East Asian | 27% | 4 |
| Finnish (not grpmax-eligible) | 21.7% | 5 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**MAP4** population constraint: LOEUF 0.512, pLI 0.13681, missense-Z 2.4555. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **628** lies in a UniProt-annotated variant site (in).

AlphaFold model confidence (whole protein): pLDDT 43.03, 0% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of MAP4 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** MAP4's established molecular role includes RNA binding.


### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA binding, microtubule stabilizing activity.

**Biological process:** microtubule cytoskeleton organization, mitotic spindle organization, microtubule polymerization, microtubule sliding, establishment of spindle orientation, cell division.

## Clinical significance {#significance}

**Benign** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2019-10-25.

**Submitter consensus:** unanimous (1/1 Benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| PreventionGenetics, part of Exact Sciences | Benign | no assertion criteria provided | clinical testing | 2019-10-25 |

## Associated conditions {#conditions}

[MAP4-related disorder](https://sugi.bio/atlas/disease/map4-related-disorder/).

**Reported phenotype names (ClinVar):** MAP4-related disorder, MAP4-related condition.

## Similar variants {#similar}

Related MAP4 variant pages (same residue, condition, or type): [MAP4 p.Val628=](/variant/map4-p-val628), [MAP4 p.Val628Ala](/variant/map4-p-val628ala), [MAP4 c.292+2409G>A](/variant/map4-c-292-plus-2409g-a), [MAP4 c.*100G>A](/variant/map4-c-star-100g-a), [MAP4 c.*44G>A](/variant/map4-c-star-44g-a), [MAP4 p.Ala2123=](/variant/map4-p-ala2123), [MAP4 p.Ala2134=](/variant/map4-p-ala2134), [MAP4 p.Ala437=](/variant/map4-p-ala437).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3060070). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*