Is CD81 p.Thr96Asn (c.287C>A) pathogenic?

CD81 p.Thr96Asn (c.287C>A) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.9109); Very rare (popmax 8.47e-05%, nfe).

How common is CD81 p.Thr96Asn (c.287C>A) in the general population?

CD81 p.Thr96Asn (c.287C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD81 p.Thr96Asn (c.287C>A)?

AlphaMissense predicts likely pathogenic (score 0.9109) — an in-silico prediction, not a clinical call.

CD81 p.Thr96Asn

c.287C>A · VCV4223043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9109	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -15.25	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,682 bp · p 0.22 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.85e-05% 1/1,460,454 alleles · very rare

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.Thr96Asn
Coding: c.287C>A
MANE Select: NM_004356
Type: single nucleotide variant
Location: chr11:2394979 (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.Thr96= Benign/Likely benign ★★ same residue
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

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-thr96asn (accessed [today's date]).

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