Is CD80 p.Val45Leu (c.133G>C) pathogenic?

CD80 p.Val45Leu (c.133G>C) is classified Uncertain significance in CD80 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1883); Absent from gnomAD v4.1.

How common is CD80 p.Val45Leu (c.133G>C) in the general population?

CD80 p.Val45Leu (c.133G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD80 p.Val45Leu (c.133G>C)?

AlphaMissense predicts likely benign (score 0.1883) — an in-silico prediction, not a clinical call.

CD80 p.Val45Leu

c.133G>C · VCV4650709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1883 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1883	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -6.37	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 -1.1	GERP -4.3
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.00015 · regional, not allelic
Overall
CADD	1.603	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD80
Protein: p.Val45Leu
Coding: c.133G>C
MANE Select: NM_005191
Type: single nucleotide variant
Location: chr3:119544835 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 6 PDB
Residue 45: 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.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-val45leu (accessed [today's date]).

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