Is CD81 p.Thr42Ile (c.125C>T) pathogenic?

CD81 p.Thr42Ile (c.125C>T) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: likely pathogenic (0.6493); Absent from gnomAD v4.1.

How common is CD81 p.Thr42Ile (c.125C>T) in the general population?

CD81 p.Thr42Ile (c.125C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD81 p.Thr42Ile (c.125C>T)?

AlphaMissense predicts likely pathogenic (score 0.6493) — an in-silico prediction, not a clinical call.

CD81 p.Thr42Ile

c.125C>T · VCV3829638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6493 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6493	likely pathogenic
REVEL	0.146	moderately benign-leaning
SaProt	LLR -10.41	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.58, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	25.9	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

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.Thr42Ile
Coding: c.125C>T
MANE Select: NM_004356
Type: single nucleotide variant
Location: chr11:2390470 (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.Thr42Ala Uncertain significance ★ ⚠ same residue
CD81 p.Thr42= 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

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-thr42ile (accessed [today's date]).

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