Is CD86 p.Met83Val (c.247A>G) pathogenic?

CD86 p.Met83Val (c.247A>G) is classified Uncertain significance in CD86 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-01-22). AlphaMissense: likely benign (0.0751); Ultra-rare (popmax 0.0112%, nfe).

How common is CD86 p.Met83Val (c.247A>G) in the general population?

CD86 p.Met83Val (c.247A>G) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about CD86 p.Met83Val (c.247A>G)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

CD86 p.Met83Val

c.247A>G · rs35276006 · VCV2366783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -3.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.8, phastCons 0.001
Regional constraint	o/e 0.90	unconstrained · MANE · 64 kb · p 0.048 · regional, not allelic
Overall
CADD	15.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0112% European (non-Finnish) · 132/1,179,950 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00836% 135/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,939
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: CD86
Protein: p.Met83Val
Coding: c.247A>G
MANE Select: NM_175862
dbSNP: rs35276006
Type: single nucleotide variant
Location: chr3:122103694 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 7 PDB
Residue 83: a disulfide bond; the ig-like v-type domain

Full CD86 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD86 p.Met83Ile Uncertain significance ★ ⚠ same residue
CD86 p.Met83Thr Uncertain significance ★ ⚠ same residue
CD86 p.Ala310Thr Benign ★★ same type
CD86 p.Asp323Asn Benign ★★ same type
CD86 p.Ala24Val Uncertain significance ★ ⚠ same type
CD86 p.Arg277Cys Uncertain significance ★ ⚠ same type
CD86 p.Arg277His Uncertain significance ★ ⚠ same type
CD86 p.Arg306Ile 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/cd86-p-met83val (accessed [today's date]).

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