Is CD86 p.Glu73Gly (c.218A>G) pathogenic?

CD86 p.Glu73Gly (c.218A>G) is classified Uncertain significance in CD86 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.2247); Ultra-rare (popmax 0.0746%, afr).

How common is CD86 p.Glu73Gly (c.218A>G) in the general population?

CD86 p.Glu73Gly (c.218A>G) is ultra-rare (popmax 0.0746%, afr) (gnomAD).

What do computational predictors say about CD86 p.Glu73Gly (c.218A>G)?

AlphaMissense predicts likely benign (score 0.2247) — an in-silico prediction, not a clinical call.

CD86 p.Glu73Gly

c.218A>G · rs146192611 · VCV3140696

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2247 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0746%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2247	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 0.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 64 kb · p 0.048 · regional, not allelic
Overall
CADD	24.0	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 0.0746% African / African-American · 56/75,050 alleles

Filtering AF 0.0589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.0044% 71/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0746%	1,340
Admixed American	0.0183%	5,456
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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.Glu73Gly
Coding: c.218A>G
MANE Select: NM_175862
dbSNP: rs146192611
Type: single nucleotide variant
Location: chr3:122103665 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 7 PDB
Residue 73: a disulfide bond; a β-strand; the ig-like v-type domain

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

Similar variants

CD86 p.Glu73Gln 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
CD86 p.Asp104Glu 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-glu73gly (accessed [today's date]).

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