# NM_001290043.2(TAP2):c.1800A>C (p.Val600=)

https://sugi.bio/variant/tap2-p-val600

## Summary

**TAP2 p.Val600= (c.1800A>C)** is classified **Benign** in TAP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with MHC class I deficiency.

**At a glance:** Benign · review: Multiple submitters · rsID rs2229527 · 4 submitters · 1 linked condition · common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele

## For patients & families {#patients}

This is a change in the TAP2 gene that is classified as benign — not considered disease-causing, submitted by 4 submitters, and is linked to MHC class I deficiency.

*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.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal recessive |
| Age of onset (of this condition) | Childhood |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0009548/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TAP2](https://sugi.bio/atlas/gene/TAP2/) |
| Protein change (HGVS p.) | p.Val600= |
| Coding change (HGVS c.) | c.1800A>C |
| MANE Select transcript | [NM_001290043](https://www.ncbi.nlm.nih.gov/nuccore/NM_001290043) |
| dbSNP | [rs2229527](https://www.ncbi.nlm.nih.gov/snp/rs2229527/) |
| Variant type | single nucleotide variant |
| Location | chr6:32829532-32829532 (GRCh38) |
| ClinVar | [VCV403514](https://www.ncbi.nlm.nih.gov/clinvar/variation/403514/) |

**All HGVS expressions:** `LRG_167:g.14239A>C`, `LRG_167t1:c.1800A>C`, `LRG_167t2:c.1800A>C`, `NC_000006.11:g.32797309T>G`, `NC_000006.12:g.32829532T>G`, `NG_009793.4:g.14239A>C`, `NM_000544.3:c.1800A>C`, `NM_001290043.2:c.1800A>C`, `NM_018833.3:c.1800A>C`

## Computational & population evidence {#evidence}

**Concordance:** Evidence sources **disagree** — common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele.

- **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 and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor loss** (Δ 0.28) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -8.384, GERP -4.07 — fast-evolving / accelerated position
- CADD: **PHRED 0.176**. 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 deltas (raw): acceptor loss **0.28**, donor loss **0.00**, acceptor gain **0.01**, donor gain **0.00**. Largest is acceptor loss, 2 bp away.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.00**.
  Masked SpliceAI — what Ensembl VEP and the Broad lookup serve by default — is below the reporting threshold here, so those tools show **no splice signal** for this allele. Masking zeroes a loss scored against a position that is not an annotated splice site, and a gain that merely strengthens an existing one, so the raw score above is describing a cryptic site rather than the site the variant sits on. *No ACMG code is assigned either way.*
- Population frequency (gnomAD v4.1): grpmax **10.2%** (afr) · FAF95 9.96% · FAF99 9.88% · 7,613/74,988 in the highest group · 81,954/1,613,994 alleles overall — common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele.

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 10.2% | 10 |
| Finnish (not grpmax-eligible) | 9.86% | 10 |
| Amish (not grpmax-eligible) | 6.25% | 16 |
| European (non-Finnish) | 5.02% | 20 |
| East Asian | 4.54% | 22 |
| Remaining individuals (not grpmax-eligible) | 4.33% | 23 |
| Admixed American | 3.11% | 32 |
| Ashkenazi Jewish (not grpmax-eligible) | 2.94% | 34 |
| Middle Eastern | 2.66% | 38 |
| South Asian | 1.19% | 84 |

*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}


Curated gene–disease validity (ClinGen):

- **MHC class I deficiency** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 96.96, 96% of residues very-high.

**1 experimental structure(s)** (PDB): [4UYB](https://www.rcsb.org/structure/4UYB).

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2026-02-03.

**Submitter consensus:** unanimous (4/4 Benign).

**Submission history:** 4 submissions (2016–2026); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Benign | criteria provided, single submitter | clinical testing | 2016-03-28 |
| PreventionGenetics, part of Exact Sciences | Benign | no assertion criteria provided | clinical testing | 2019-07-08 |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2026-02-03 |
| Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Benign | criteria provided, single submitter | clinical testing | 2026-01-21 |

## Associated conditions {#conditions}

[MHC class I deficiency](https://sugi.bio/atlas/disease/mhc-class-i-deficiency/).

**Reported phenotype names (ClinVar):** MHC class I deficiency, not specified, TAP2-related disorder, AllHighlyPenetrant, TAP2-related condition.

## Similar variants {#similar}

Related TAP2 variant pages (same residue, condition, or type): [TAP2 c.1636-1G>A](/variant/tap2-c-1636-minus-1g-a), [TAP2 c.1932+1G>A](/variant/tap2-c-1932-plus-1g-a), [TAP2 p.Ala17Val](/variant/tap2-p-ala17val), [TAP2 p.Ala306Val](/variant/tap2-p-ala306val), [TAP2 p.Ala500Thr](/variant/tap2-p-ala500thr), [TAP2 p.Ala500Val](/variant/tap2-p-ala500val), [TAP2 p.Arg273Gln](/variant/tap2-p-arg273gln), [TAP2 p.Arg313Cys](/variant/tap2-p-arg313cys).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 2026-10-14); 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 403514). 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.*