Is CD81 p.Ala54Val (c.161C>T) pathogenic?

CD81 p.Ala54Val (c.161C>T) is classified Uncertain significance in CD81 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-21). AlphaMissense: ambiguous (0.515); Very rare (popmax 0.00432%, nfe).

How common is CD81 p.Ala54Val (c.161C>T) in the general population?

CD81 p.Ala54Val (c.161C>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about CD81 p.Ala54Val (c.161C>T)?

AlphaMissense predicts ambiguous (score 0.515) — an in-silico prediction, not a clinical call.

CD81 p.Ala54Val

c.161C>T · rs368611423 · VCV3022845

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Computational evidence

Protein change
AlphaMissense	0.515	ambiguous
REVEL	0.449	indeterminate
SaProt	LLR -7.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -0.77, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	25.1	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 0.00432% European (non-Finnish) · 51/1,179,440 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00341% 55/1,612,284 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,126
East Asian	0.00223%	44,890
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,456
South Asian	0.0011%	91,080

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.Ala54Val
Coding: c.161C>T
MANE Select: NM_004356
dbSNP: rs368611423
Type: single nucleotide variant
Location: chr11:2390506 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB

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

Similar variants

CD81 p.Ala54Thr Uncertain significance ★ ⚠ same residue
CD81 p.Ala54= Likely benign ★ same residue
CD81 c.561+5G>A Uncertain significance ★★ same type
CD81 p.Ala120Thr 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

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-ala54val (accessed [today's date]).

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