Is CD82 p.Val143Met (c.427G>A) pathogenic?

CD82 p.Val143Met (c.427G>A) is classified Uncertain significance in CD82 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-30). AlphaMissense: ambiguous (0.4607); Ultra-rare (popmax 0.0241%, nfe).

How common is CD82 p.Val143Met (c.427G>A) in the general population?

CD82 p.Val143Met (c.427G>A) is ultra-rare (popmax 0.0241%, nfe) (gnomAD).

What do computational predictors say about CD82 p.Val143Met (c.427G>A)?

AlphaMissense predicts ambiguous (score 0.4607) — an in-silico prediction, not a clinical call.

CD82 p.Val143Met

c.427G>A · VCV3488187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4607 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4607	ambiguous
REVEL	0.644	pathogenic-leaning
SaProt	LLR -8.04	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.71 · regional, not allelic
Overall
CADD	26.6	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 0.0241% European (non-Finnish) · 283/1,174,596 alleles

Filtering AF 0.0217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.0193% 310/1,607,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0321%	3,113
European (non-Finnish)grpmax	0.0241%	4,151
African / African-American	0.00401%	24,931
East Asian	0.00223%	44,858
South Asian	0.0022%	45,486
Admixed American	0.00167%	59,996

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val143Met
Coding: c.427G>A
MANE Select: NM_002231
Type: single nucleotide variant
Location: chr11:44615362 (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-val143met (accessed [today's date]).

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