Is CD82 p.Arg254Trp (c.760C>T) pathogenic?

CD82 p.Arg254Trp (c.760C>T) is classified Uncertain significance in CD82 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.2155); Ultra-rare (popmax 0.0395%, sas).

How common is CD82 p.Arg254Trp (c.760C>T) in the general population?

CD82 p.Arg254Trp (c.760C>T) is ultra-rare (popmax 0.0395%, sas) (gnomAD).

What do computational predictors say about CD82 p.Arg254Trp (c.760C>T)?

AlphaMissense predicts likely benign (score 0.2155) — an in-silico prediction, not a clinical call.

CD82 p.Arg254Trp

c.760C>T · rs201405906 · VCV3336817

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2155	likely benign
REVEL	0.765	pathogenic-leaning
SaProt	LLR -9.37	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.71 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% South Asian · 36/91,054 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.0218% 351/1,613,398 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0395%	2,529
East Asian	0.0357%	2,798
European (non-Finnish)	0.0236%	4,229
Remaining individualsnot grpmax-eligible	0.016%	6,250
African / African-American	0.0107%	9,350
Admixed American	0.00333%	29,991

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: CD82
Protein: p.Arg254Trp
Coding: c.760C>T
MANE Select: NM_002231
dbSNP: rs201405906
Type: single nucleotide variant
Location: chr11:44619082 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.31 · 1 PDB

Full CD82 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD82 p.Gly233= Benign ★★ same type
CD82 p.Leu248= Benign ★★ same type
CD82 p.Val62= Benign ★★ same type
CD82 p.Ala195Val Uncertain significance ★ ⚠ same type
CD82 p.Arg53Ser Uncertain significance ★ ⚠ same type
CD82 p.Asn109Ser Uncertain significance ★ ⚠ same type
CD82 p.Asn17Ser Uncertain significance ★ ⚠ same type
CD82 p.Asn227Thr Uncertain significance ★ ⚠ same type

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/cd82-p-arg254trp (accessed [today's date]).

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