Is CD80 p.Arg286His (c.857G>A) pathogenic?

CD80 p.Arg286His (c.857G>A) is classified Uncertain significance in CD80 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.1198); Very rare (popmax 0.00271%, nfe).

How common is CD80 p.Arg286His (c.857G>A) in the general population?

CD80 p.Arg286His (c.857G>A) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about CD80 p.Arg286His (c.857G>A)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

CD80 p.Arg286His

c.857G>A · VCV3829635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.14	GERP -3.8
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.00015 · regional, not allelic
Overall
CADD	15.86	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 0.00271% European (non-Finnish) · 32/1,179,622 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00217% 35/1,613,538 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,863
Admixed American	0.00167%	59,990
African / African-American	0.00134%	74,882
South Asian	0.0011%	91,072

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: CD80
Protein: p.Arg286His
Coding: c.857G>A
MANE Select: NM_005191
Type: single nucleotide variant
Location: chr3:119527781 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 6 PDB

Full CD80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD80 p.Arg286Cys Uncertain significance ★ ⚠ same residue
CD80 c.*214T>G Benign ★★ same type
CD80 p.His222Tyr Benign ★★ ⚠ same type
CD80 p.Arg107His Uncertain significance ★ ⚠ same type
CD80 p.Arg128Gln Uncertain significance ★ ⚠ same type
CD80 p.Arg224Lys Uncertain significance ★ ⚠ same type
CD80 p.Arg63Cys Uncertain significance ★ ⚠ same type
CD80 p.Asn183Asp 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/cd80-p-arg286his (accessed [today's date]).

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