# NM_018136.5(ASPM):c.2377C>A (p.Arg793=)

https://sugi.bio/variant/aspm-p-arg793

## Summary

**ASPM p.Arg793= (c.2377C>A)** is classified **Likely benign** in ASPM (ClinVar, Single submitter, 1 submitter; last evaluated 2018-04-04). Very rare (popmax 0.00534%, afr).

**At a glance:** Likely benign · review: Single submitter · rsID rs779018406 · 1 submitter · very rare (popmax 0.00534%, afr)

## For patients & families {#patients}

This is a change in the ASPM gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*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 | [ASPM](https://sugi.bio/atlas/gene/ASPM/) |
| Protein change (HGVS p.) | p.Arg793= |
| Coding change (HGVS c.) | c.2377C>A |
| MANE Select transcript | [NM_018136](https://www.ncbi.nlm.nih.gov/nuccore/NM_018136) |
| dbSNP | [rs779018406](https://www.ncbi.nlm.nih.gov/snp/rs779018406/) |
| Variant type | single nucleotide variant |
| Location | chr1:197133392-197133392 (GRCh38) |
| ClinVar | [VCV747224](https://www.ncbi.nlm.nih.gov/clinvar/variation/747224/) |

**All HGVS expressions:** `NC_000001.10:g.197102522G>T`, `NC_000001.11:g.197133392G>T`, `NG_015867.1:g.18303C>A`, `NM_001206846.2:c.2377C>A`, `NM_018136.5:c.2377C>A`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 3.458, GERP 0.061, phastCons 1 — highly conserved position (PP3-type support)
- CADD: **PHRED 6.719**. 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.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (G>C, Δ0.36 donor loss), 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 **0.00534%** (afr) · FAF95 0.00175% · FAF99 0.00104% · 4/74,852 in the highest group · 7/1,613,646 alleles overall — very rare (popmax 0.00534%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 0.00534% | 18,713 |
| European (non-Finnish) | 0.000254% | 393,284 |

*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}

**ASPM** population constraint: LOEUF 0.766, pLI 3.3385e-55, missense-Z 0.80711; ClinGen dosage — haploinsufficiency 30, triplosensitivity 0 (0–3 scale). *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **autosomal recessive primary microcephaly** — Definitive (AR)

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2018-04-04.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2018-04-04 |

**Reported phenotype names (ClinVar):** not provided, none provided, RECLASSIFIED - ADRA2C POLYMORPHISM, RECLASSIFIED - ADRB1 POLYMORPHISM.

## Similar variants {#similar}

Related ASPM variant pages (same residue, condition, or type): [ASPM p.Arg793Gln](/variant/aspm-p-arg793gln), [ASPM p.Arg793Trp](/variant/aspm-p-arg793trp), [ASPM c.2419+2T>C](/variant/aspm-c-2419-plus-2t-c), [ASPM c.2488-1G>C](/variant/aspm-c-2488-minus-1g-c), [ASPM c.2936+5G>A](/variant/aspm-c-2936-plus-5g-a), [ASPM c.3082+1G>C](/variant/aspm-c-3082-plus-1g-c), [ASPM c.9084+5G>A](/variant/aspm-c-9084-plus-5g-a), [ASPM p.Arg1019Ter](/variant/aspm-p-arg1019ter).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 747224). 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.*