Is CD81 p.Asp137Asn (c.409G>A) pathogenic?

CD81 p.Asp137Asn (c.409G>A) is classified Uncertain significance in CD81 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.0849); Ultra-rare (popmax 0.0263%, nfe); Associated with immunodeficiency, common variable, 6.

What condition is associated with CD81 p.Asp137Asn (c.409G>A)?

CD81 p.Asp137Asn (c.409G>A) is associated with immunodeficiency, common variable, 6 (ClinVar).

How common is CD81 p.Asp137Asn (c.409G>A) in the general population?

CD81 p.Asp137Asn (c.409G>A) is ultra-rare (popmax 0.0263%, nfe) (gnomAD).

What do computational predictors say about CD81 p.Asp137Asn (c.409G>A)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

CD81 p.Asp137Asn

c.409G>A · rs767263004 · VCV1347538

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0263%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency, common variable, 6

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -2.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,682 bp · p 0.22 · regional, not allelic
Overall
CADD	18.99	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0263% European (non-Finnish) · 310/1,179,928 alleles

Filtering AF 0.0238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0197% 318/1,612,704 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0263%	3,806
Remaining individualsnot grpmax-eligible	0.008%	12,492
African / African-American	0.004%	24,975

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.Asp137Asn
Coding: c.409G>A
MANE Select: NM_004356
dbSNP: rs767263004
Type: single nucleotide variant
Location: chr11:2395470 (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

Disease context

immunodeficiency, common variable, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD81 p.Asp137= Likely benign ★★ same residue
CD81 p.Asn141Lys Uncertain significance ★★ ⚠ same condition
CD81 p.Asp195Asn Uncertain significance ★★ ⚠ same condition
CD81 c.459+4C>T Benign/Likely benign ★★ same condition
CD81 c.648+10C>T Benign/Likely benign ★★ same condition
CD81 p.Asp138= Benign/Likely benign ★★ same condition
CD81 p.Pro53= Likely benign ★★ same condition
CD81 p.Ser199= Benign ★★ 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/cd81-p-asp137asn (accessed [today's date]).

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