Is CD81 p.Ile210Phe (c.628A>T) pathogenic?

CD81 p.Ile210Phe (c.628A>T) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.5796); Absent from gnomAD v4.1.

How common is CD81 p.Ile210Phe (c.628A>T) in the general population?

CD81 p.Ile210Phe (c.628A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD81 p.Ile210Phe (c.628A>T)?

AlphaMissense predicts likely pathogenic (score 0.5796) — an in-silico prediction, not a clinical call.

CD81 p.Ile210Phe

c.628A>T · VCV4730361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5796 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5796	likely pathogenic
REVEL	0.561	indeterminate
SaProt	LLR -10.79	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 6.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,682 bp · p 0.22 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD81
Protein: p.Ile210Phe
Coding: c.628A>T
MANE Select: NM_004356
Type: single nucleotide variant
Location: chr11:2396694 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 210: an α-helix

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

Similar variants

CD81 p.Ile210= 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-ile210phe (accessed [today's date]).

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