Is CD81 p.Phe17Leu (c.49T>C) pathogenic?

CD81 p.Phe17Leu (c.49T>C) is classified Uncertain significance in CD81 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9412); Very rare (popmax 0.00369%, amr).

How common is CD81 p.Phe17Leu (c.49T>C) in the general population?

CD81 p.Phe17Leu (c.49T>C) is very rare (popmax 0.00369%, amr) (gnomAD).

What do computational predictors say about CD81 p.Phe17Leu (c.49T>C)?

AlphaMissense predicts likely pathogenic (score 0.9412) — an in-silico prediction, not a clinical call.

CD81 p.Phe17Leu

c.49T>C · rs1046814935 · VCV2889092

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9412 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00369%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9412	likely pathogenic
REVEL	0.279	benign-leaning
SaProt	LLR -11.25	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 5.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.15 · regional, not allelic
Overall
CADD	23.7	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 0.00369% Admixed American · 2/54,134 alleles

Filtering AF 0.000613% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000229%

Overall 0.000324% 5/1,543,284 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00369%	27,067
African / African-American	0.00285%	35,149
European (non-Finnish)	8.75e-05%	1,142,509

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.Phe17Leu
Coding: c.49T>C
MANE Select: NM_004356
dbSNP: rs1046814935
Type: single nucleotide variant
Location: chr11:2377598 (GRCh38)
Gene constraint: LOEUF 0.702 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 87.24 · 16 PDB
Residue 17: an α-helix

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

Similar variants

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
CD81 p.Asn173Asp 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-phe17leu (accessed [today's date]).

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