Is CD82 p.Leu124Phe (c.370C>T) pathogenic?

CD82 p.Leu124Phe (c.370C>T) is classified Uncertain significance in CD82 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: ambiguous (0.423); Very rare (popmax 0.00687%, nfe).

How common is CD82 p.Leu124Phe (c.370C>T) in the general population?

CD82 p.Leu124Phe (c.370C>T) is very rare (popmax 0.00687%, nfe) (gnomAD).

What do computational predictors say about CD82 p.Leu124Phe (c.370C>T)?

AlphaMissense predicts ambiguous (score 0.423) — an in-silico prediction, not a clinical call.

CD82 p.Leu124Phe

c.370C>T · VCV3488184

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.423 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.423	ambiguous
REVEL	0.18	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.05	GERP -2.7, phastCons 0.001
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.71 · regional, not allelic
Overall
CADD	12.21	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 0.00687% European (non-Finnish) · 81/1,179,324 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00527% 85/1,613,268 alleles · very rare exomes 77/1,461,074 · genomes 8/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00687%	14,560
Remaining individualsnot grpmax-eligible	0.0064%	15,615

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: CD82
Protein: p.Leu124Phe
Coding: c.370C>T
MANE Select: NM_002231
Type: single nucleotide variant
Location: chr11:44615305 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.31 · 1 PDB

Full CD82 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD82 p.Gly233= Benign ★★ same type
CD82 p.Leu248= Benign ★★ same type
CD82 p.Val62= Benign ★★ same type
CD82 p.Ala195Val Uncertain significance ★ ⚠ same type
CD82 p.Arg254Trp Uncertain significance ★ ⚠ same type
CD82 p.Arg53Ser Uncertain significance ★ same type
CD82 p.Asn109Ser Uncertain significance ★ ⚠ same type
CD82 p.Asn17Ser 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/cd82-p-leu124phe (accessed [today's date]).

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