Is CD86 p.Arg312His (c.935G>A) pathogenic?

CD86 p.Arg312His (c.935G>A) is classified Likely benign in CD86 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-21). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.012%, afr).

How common is CD86 p.Arg312His (c.935G>A) in the general population?

CD86 p.Arg312His (c.935G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CD86 p.Arg312His (c.935G>A)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

CD86 p.Arg312His

c.935G>A · rs370380261 · VCV2392164

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.19	GERP -3.1
Regional constraint	o/e 0.90	unconstrained · MANE · 64 kb · p 0.048 · regional, not allelic
Overall
CADD	0.391	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 0.012% African / African-American · 9/74,870 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00211% 34/1,611,724 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,319
South Asian	0.0066%	15,162
Remaining individualsnot grpmax-eligible	0.0032%	31,208
East Asian	0.00223%	44,864
Admixed American	0.00167%	59,984
European (non-Finnish)	0.00127%	78,535

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.Arg312His
Coding: c.935G>A
MANE Select: NM_175862
dbSNP: rs370380261
Type: single nucleotide variant
Location: chr3:122119479 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 80.10 · 7 PDB
Residue 312: the 'disordered' region

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

Similar variants

CD86 p.Arg312Cys Likely benign ★ 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-arg312his (accessed [today's date]).

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