Is CD86 p.Val199Ile (c.595G>A) pathogenic?

CD86 p.Val199Ile (c.595G>A) is classified Uncertain significance in CD86 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0878); Very rare (popmax 0.00667%, amr).

How common is CD86 p.Val199Ile (c.595G>A) in the general population?

CD86 p.Val199Ile (c.595G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CD86 p.Val199Ile (c.595G>A)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

CD86 p.Val199Ile

c.595G>A · VCV3488201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -7.69	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 1.3	GERP -1.2, phastCons 0.78
Regional constraint	o/e 0.90	unconstrained · MANE · 64 kb · p 0.048 · regional, not allelic
Overall
CADD	14.56	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 0.00667% Admixed American · 4/60,006 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00155% 25/1,613,868 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,002
South Asian	0.00659%	15,181
African / African-American	0.00267%	37,458
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.00102%	98,322

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.Val199Ile
Coding: c.595G>A
MANE Select: NM_175862
Type: single nucleotide variant
Location: chr3:122106392 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 7 PDB
Residue 199: a disulfide bond; the ig-like c2-type domain

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

Similar variants

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
CD86 p.Asp104Glu Uncertain significance ★ ⚠ same type
CD86 p.Gln311Glu 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-val199ile (accessed [today's date]).

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