Is CD81 p.Thr42Ala (c.124A>G) pathogenic?

CD81 p.Thr42Ala (c.124A>G) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-19). AlphaMissense: likely benign (0.1538); Very rare (popmax 0.0011%, nfe).

How common is CD81 p.Thr42Ala (c.124A>G) in the general population?

CD81 p.Thr42Ala (c.124A>G) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about CD81 p.Thr42Ala (c.124A>G)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

CD81 p.Thr42Ala

c.124A>G · rs759382182 · VCV1953783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.56	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	23.0	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 0.0011% European (non-Finnish) · 13/1,180,018 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00089% 13/1,460,622 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.Thr42Ala
Coding: c.124A>G
MANE Select: NM_004356
dbSNP: rs759382182
Type: single nucleotide variant
Location: chr11:2390469 (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.Thr42Ile 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-thr42ala (accessed [today's date]).

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