Is CD80 p.Arg128Gln (c.383G>A) pathogenic?

CD80 p.Arg128Gln (c.383G>A) is classified Uncertain significance in CD80 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). AlphaMissense: likely benign (0.132); Very rare (popmax 0.00667%, afr).

How common is CD80 p.Arg128Gln (c.383G>A) in the general population?

CD80 p.Arg128Gln (c.383G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about CD80 p.Arg128Gln (c.383G>A)?

AlphaMissense predicts likely benign (score 0.132) — an in-silico prediction, not a clinical call.

CD80 p.Arg128Gln

c.383G>A · rs770820543 · VCV3140672

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.132	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -6.01	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 -2.3	GERP -4.5
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.00015 · regional, not allelic
Overall
CADD	10.94	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% African / African-American · 5/74,926 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.0018% 29/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,985
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00223%	44,896
Admixed American	0.00167%	59,994
European (non-Finnish)	0.00161%	62,103

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.Arg128Gln
Coding: c.383G>A
MANE Select: NM_005191
dbSNP: rs770820543
Type: single nucleotide variant
Location: chr3:119544585 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 6 PDB
Residue 128: a β-strand; the ig-like v-type domain

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

Similar variants

CD80 c.*214T>G Benign ★★ same type
CD80 p.His222Tyr Benign ★★ ⚠ same type
CD80 p.Arg107His Uncertain significance ★ ⚠ same type
CD80 p.Arg224Lys Uncertain significance ★ ⚠ same type
CD80 p.Arg286Cys Uncertain significance ★ ⚠ same type
CD80 p.Arg286His 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-arg128gln (accessed [today's date]).

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