Is CD81 p.Ser177Leu (c.530C>T) pathogenic?

CD81 p.Ser177Leu (c.530C>T) is classified Uncertain significance in CD81 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). AlphaMissense: likely benign (0.1434); Very rare (popmax 0.00446%, eas).

How common is CD81 p.Ser177Leu (c.530C>T) in the general population?

CD81 p.Ser177Leu (c.530C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CD81 p.Ser177Leu (c.530C>T)?

AlphaMissense predicts likely benign (score 0.1434) — an in-silico prediction, not a clinical call.

CD81 p.Ser177Leu

c.530C>T · rs960741214 · VCV2897905

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1434 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1434	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -12.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.2	GERP 1.4, phastCons 0.17
Regional constraint	o/e 0.91	unconstrained · MANE · 2,682 bp · p 0.22 · regional, not allelic
Overall
CADD	17.19	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

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000993% 16/1,611,864 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
South Asian	0.0022%	45,539
Remaining individualsnot grpmax-eligible	0.0016%	62,444
European (non-Finnish)	0.000848%	117,936

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.Ser177Leu
Coding: c.530C>T
MANE Select: NM_004356
dbSNP: rs960741214
Type: single nucleotide variant
Location: chr11:2395939 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 177: a disulfide bond

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

Similar variants

CD81 p.Ser177= 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-ser177leu (accessed [today's date]).

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