Is CD80 p.Gly27Asp (c.80G>A) pathogenic?

CD80 p.Gly27Asp (c.80G>A) is classified Uncertain significance in CD80 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: ambiguous (0.3548); Very rare (popmax 0.00167%, amr).

How common is CD80 p.Gly27Asp (c.80G>A) in the general population?

CD80 p.Gly27Asp (c.80G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD80 p.Gly27Asp (c.80G>A)?

AlphaMissense predicts ambiguous (score 0.3548) — an in-silico prediction, not a clinical call.

CD80 p.Gly27Asp

c.80G>A · VCV4223040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3548	ambiguous
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.49	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -3.4
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.00015 · regional, not allelic
Overall
CADD	14.57	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 0.00167% Admixed American · 1/59,980 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 10/1,461,110 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
European (non-Finnish)	0.000763%	131,068

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.Gly27Asp
Coding: c.80G>A
MANE Select: NM_005191
Type: single nucleotide variant
Location: chr3:119557649 (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 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.Arg286Cys Uncertain significance ★ ⚠ same type
CD80 p.Arg286His Uncertain significance ★ ⚠ same type
CD80 p.Arg63Cys 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-gly27asp (accessed [today's date]).

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