Is TAP1 p.His155= (c.465C>T) pathogenic?

TAP1 p.His155= (c.465C>T) is classified Benign/Likely benign in TAP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Low-frequency (popmax 1.68%, eas); Associated with MHC class I deficiency.

What condition is associated with TAP1 p.His155= (c.465C>T)?

TAP1 p.His155= (c.465C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP1 p.His155= (c.465C>T) in the general population?

TAP1 p.His155= (c.465C>T) is low-frequency (popmax 1.68%, eas) (gnomAD).

TAP1 p.His155=

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.465C>T · rs56016563 · VCV534723

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, eas)

Conditions

MHC class I deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP -0.72, phastCons 0.007
Overall
CADD	8.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.68% East Asian · 756/44,884 alleles

Filtering AF 1.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.55%

Overall 0.0564% 910/1,612,642 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.68%	59
Finnishnot grpmax-eligible	0.113%	886
Remaining individualsnot grpmax-eligible	0.0624%	1,602
South Asian	0.0187%	5,351
African / African-American	0.00666%	15,012
Admixed American	0.00334%	29,981
European (non-Finnish)	0.0017%	58,994

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.His155=
Coding: c.465C>T
MANE Select: NM_000593
dbSNP: rs56016563
Type: single nucleotide variant
Location: chr6:32853172 (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

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-his155 (accessed [today's date]).

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