Is TAP2 p.Ser418= (c.1254C>T) pathogenic?

TAP2 p.Ser418= (c.1254C>T) is classified Likely benign in TAP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). Ultra-rare (popmax 0.0495%, mid); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Ser418= (c.1254C>T)?

TAP2 p.Ser418= (c.1254C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Ser418= (c.1254C>T) in the general population?

TAP2 p.Ser418= (c.1254C>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

TAP2 p.Ser418=

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.1254C>T · rs771248316 · VCV2163726

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

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 -3.4	GERP -3.8
Overall
CADD	0.411	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,066 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00717%

Overall 0.00105% 17/1,612,824 alleles · ultra-rare exomes 16/1,460,708 · genomes 1/152,116 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,022
African / African-American	0.00401%	24,963
South Asian	0.0022%	45,532
Remaining individualsnot grpmax-eligible	0.0016%	62,476
European (non-Finnish)	0.000678%	147,502

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: TAP2
Protein: p.Ser418=
Coding: c.1254C>T
MANE Select: NM_001290043
dbSNP: rs771248316
Type: single nucleotide variant
Location: chr6:32832351 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB

Full TAP2 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

TAP2 c.1636-1G>A Pathogenic/Likely pathogenic ★★ same condition
TAP2 c.1932+1G>A Uncertain significance ★★ same condition
TAP2 p.Ala17Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala306Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Thr Uncertain significance ★★ ⚠ same condition
TAP2 p.Ala500Val Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg273Gln Uncertain significance ★★ ⚠ same condition
TAP2 p.Arg313Cys 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/tap2-p-ser418 (accessed [today's date]).

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