Is TAP1 p.Pro7Ser (c.19C>T) pathogenic?

TAP1 p.Pro7Ser (c.19C>T) is classified Uncertain significance in TAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-13). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.0822%, mid); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.Pro7Ser (c.19C>T)?

TAP1 p.Pro7Ser (c.19C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.Pro7Ser (c.19C>T) in the general population?

TAP1 p.Pro7Ser (c.19C>T) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about TAP1 p.Pro7Ser (c.19C>T)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

TAP1 p.Pro7Ser

Q: How is Immunodeficiency by defective expression of MHC class I inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.19C>T · rs375389015 · VCV582649

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

MHC class I deficiency

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.243	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.23, phastCons 0.42
Overall
CADD	12.46	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P67S vs ClinVar P7S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0822% Middle Eastern · 5/6,080 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00577% 93/1,611,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,216
African / African-American	0.0547%	1,827
Remaining individualsnot grpmax-eligible	0.0368%	2,714
South Asian	0.0143%	7,004
Admixed American	0.005%	19,995
European (non-Finnish)	0.000678%	147,466

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TAP1
Protein: p.Pro7Ser
Coding: c.19C>T
MANE Select: NM_000593
dbSNP: rs375389015
Type: single nucleotide variant
Location: chr6:32853618 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 22 PDB
Residue 7: a UniProt-annotated variant site (in)

Full TAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MHC class I deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency by defective expression of MHC class I (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

TAP1 p.Arg378Ter Pathogenic ★★ same condition
TAP1 p.Gln522Ter Pathogenic/Likely pathogenic ★★ same condition
TAP1 c.-20G>C Uncertain significance ★★ ⚠ same condition
TAP1 c.-59C>T Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala101Val Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Ala59Thr Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg129Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tap1-p-pro7ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown