Is TAP1 p.Pro41Ser (c.121C>T) pathogenic?

TAP1 p.Pro41Ser (c.121C>T) is classified Uncertain significance in TAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: likely benign (0.2316); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with TAP1 p.Pro41Ser (c.121C>T)?

TAP1 p.Pro41Ser (c.121C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TAP1 p.Pro41Ser (c.121C>T) in the general population?

TAP1 p.Pro41Ser (c.121C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about TAP1 p.Pro41Ser (c.121C>T)?

AlphaMissense predicts likely benign (score 0.2316) — an in-silico prediction, not a clinical call.

TAP1 p.Pro41Ser

c.121C>T · VCV4179982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2316	likely benign
REVEL	0.314	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.15, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P101S vs ClinVar P41S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,840 alleles

Overall 0.000124% 2/1,609,632 alleles · very rare exomes 1/1,457,396 · genomes 1/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,840
European (non-Finnish)	8.49e-05%	1,177,550

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.Pro41Ser
Coding: c.121C>T
MANE Select: NM_000593
Type: single nucleotide variant
Location: chr6:32853516 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 22 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAP1 c.-20G>C Uncertain significance ★★ ⚠ same condition
TAP1 c.-59C>T 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
TAP1 p.Arg575Cys Uncertain significance ★★ ⚠ same condition
TAP1 p.Arg659Trp Uncertain significance ★★ ⚠ same condition
TAP1 p.Asn401Lys 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-pro41ser (accessed [today's date]).

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