Is CD226 p.Pro210Arg (c.629C>G) pathogenic?

CD226 p.Pro210Arg (c.629C>G) is classified Uncertain significance in CD226 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.1703); Absent from gnomAD v4.1.

How common is CD226 p.Pro210Arg (c.629C>G) in the general population?

CD226 p.Pro210Arg (c.629C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD226 p.Pro210Arg (c.629C>G)?

AlphaMissense predicts likely benign (score 0.1703) — an in-silico prediction, not a clinical call.

CD226 p.Pro210Arg

c.629C>G · VCV4650536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1703 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1703	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -9.06	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 1.8	GERP 1.6, phastCons 0.96
Regional constraint	o/e 0.96	unconstrained · MANE · 83 kb · p 0.44 · regional, not allelic
Overall
CADD	14.63	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: CD226
Protein: p.Pro210Arg
Coding: c.629C>G
MANE Select: NM_001303618
Type: single nucleotide variant
Location: chr18:69895799 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.75 · 2 PDB
Residue 210: a disulfide bond; the ig-like c2-type 2 domain

Full CD226 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD226 p.Ala133Val Uncertain significance ★ ⚠ same type
CD226 p.Ala16Gly Uncertain significance ★ ⚠ same type
CD226 p.Ala226Thr Uncertain significance ★ ⚠ same type
CD226 p.Ala76Thr Uncertain significance ★ ⚠ same type
CD226 p.Ala76Val Uncertain significance ★ ⚠ same type
CD226 p.Ala9Pro Uncertain significance ★ ⚠ same type
CD226 p.Arg193Gly Uncertain significance ★ ⚠ same type
CD226 p.Asn198Thr 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/cd226-p-pro210arg (accessed [today's date]).

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