Is CD81 p.Val211Met (c.631G>A) pathogenic?

CD81 p.Val211Met (c.631G>A) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). AlphaMissense: ambiguous (0.501); Very rare (popmax 0.00347%, nfe).

How common is CD81 p.Val211Met (c.631G>A) in the general population?

CD81 p.Val211Met (c.631G>A) is very rare (popmax 0.00347%, nfe) (gnomAD).

What do computational predictors say about CD81 p.Val211Met (c.631G>A)?

AlphaMissense predicts ambiguous (score 0.501) — an in-silico prediction, not a clinical call.

CD81 p.Val211Met

c.631G>A · rs139884987 · VCV1430335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00347%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.501	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -15.23	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,682 bp · p 0.22 · regional, not allelic
Overall
CADD	34.0	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 0.00347% European (non-Finnish) · 41/1,179,992 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00261% 42/1,611,582 alleles · very rare exomes 37/1,459,328 · genomes 5/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00347%	28,780
South Asian	0.0011%	91,096

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: CD81
Protein: p.Val211Met
Coding: c.631G>A
MANE Select: NM_004356
dbSNP: rs139884987
Type: single nucleotide variant
Location: chr11:2396697 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 211: an α-helix

Full CD81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD81 c.561+5G>A Uncertain significance ★★ same type
CD81 p.Ala120Thr Uncertain significance ★★ ⚠ same type
CD81 p.Ala54Val Uncertain significance ★★ same type
CD81 p.Arg231Gln Uncertain significance ★★ ⚠ same type
CD81 p.Asn115Ser Uncertain significance ★★ ⚠ same type
CD81 p.Asn141Lys Uncertain significance ★★ ⚠ same type
CD81 p.Asn141Ser Uncertain significance ★★ ⚠ same type
CD81 p.Asn173Asp 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/cd81-p-val211met (accessed [today's date]).

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