Is CD80 p.Ile218Thr (c.653T>C) pathogenic?

CD80 p.Ile218Thr (c.653T>C) is classified Uncertain significance in CD80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely pathogenic (0.8754); Very rare (popmax 0.00017%, nfe).

How common is CD80 p.Ile218Thr (c.653T>C) in the general population?

CD80 p.Ile218Thr (c.653T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CD80 p.Ile218Thr (c.653T>C)?

AlphaMissense predicts likely pathogenic (score 0.8754) — an in-silico prediction, not a clinical call.

CD80 p.Ile218Thr

c.653T>C · rs2473104266 · VCV2320195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8754 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8754	likely pathogenic · top 9% in CD80
REVEL	0.295	indeterminate
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 30 kb · p 0.00015 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00017% European (non-Finnish) · 2/1,179,924 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,744 alleles · very rare

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.Ile218Thr
Coding: c.653T>C
MANE Select: NM_005191
dbSNP: rs2473104266
Type: single nucleotide variant
Location: chr3:119537184 (GRCh38)
Gene constraint: LOEUF 0.818 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 6 PDB
Residue 218: a β-strand; the ig-like c2-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-ile218thr (accessed [today's date]).

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