Is TAP2 p.Ser112= (c.336C>T) pathogenic?

TAP2 p.Ser112= (c.336C>T) is classified Benign/Likely benign in TAP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-28). Low-frequency (popmax 2.34%, eas); Associated with MHC class I deficiency.

What condition is associated with TAP2 p.Ser112= (c.336C>T)?

TAP2 p.Ser112= (c.336C>T) is associated with MHC class I deficiency (ClinVar).

How common is TAP2 p.Ser112= (c.336C>T) in the general population?

TAP2 p.Ser112= (c.336C>T) is low-frequency (popmax 2.34%, eas) (gnomAD).

TAP2 p.Ser112=

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.336C>T · rs55765602 · VCV709636

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.34%, 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 4.8	GERP 1.5, phastCons 1
Overall
CADD	10.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.34% East Asian · 1,050/44,874 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.18%

Overall 0.0673% 1,085/1,613,026 alleles · low-frequency exomes 1,007/1,460,864 · genomes 78/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.34%	43
Remaining individualsnot grpmax-eligible	0.0384%	2,604
South Asian	0.00659%	15,180
Admixed American	0.00333%	30,008
European (non-Finnish)	0.000254%	393,337

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.Ser112=
Coding: c.336C>T
MANE Select: NM_001290043
dbSNP: rs55765602
Type: single nucleotide variant
Location: chr6:32837898 (GRCh38)
Structure: AlphaFold pLDDT 96.96 · 1 PDB
Residue 112: the cral-trio domain; an α-helix

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 p.Ser112Arg Uncertain significance ★ ⚠ same residue
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

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-ser112 (accessed [today's date]).

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