Is CD81 p.Arg36Cys (c.106C>T) pathogenic?

CD81 p.Arg36Cys (c.106C>T) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-07). AlphaMissense: likely pathogenic (0.9507); Very rare (popmax 0.00446%, eas).

How common is CD81 p.Arg36Cys (c.106C>T) in the general population?

CD81 p.Arg36Cys (c.106C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CD81 p.Arg36Cys (c.106C>T)?

AlphaMissense predicts likely pathogenic (score 0.9507) — an in-silico prediction, not a clinical call.

CD81 p.Arg36Cys

c.106C>T · rs772052611 · VCV1938345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9507 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9507	likely pathogenic
REVEL	0.864	moderately pathogenic-leaning
SaProt	LLR -12.84	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	33.0	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 0.00446% East Asian · 2/44,878 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000753% 11/1,460,580 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,439
South Asian	0.0022%	45,544
European (non-Finnish)	0.000593%	168,571

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.Arg36Cys
Coding: c.106C>T
MANE Select: NM_004356
dbSNP: rs772052611
Type: single nucleotide variant
Location: chr11:2390451 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 36: an α-helix

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

Similar variants

CD81 p.Arg36His Uncertain significance ★ ⚠ 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-arg36cys (accessed [today's date]).

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