Is CD226 p.Gln115Lys (c.343C>A) pathogenic?

CD226 p.Gln115Lys (c.343C>A) is classified Uncertain significance in CD226 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-28). AlphaMissense: likely benign (0.0868); Very rare (popmax 8.48e-05%, nfe).

How common is CD226 p.Gln115Lys (c.343C>A) in the general population?

CD226 p.Gln115Lys (c.343C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CD226 p.Gln115Lys (c.343C>A)?

AlphaMissense predicts likely benign (score 0.0868) — an in-silico prediction, not a clinical call.

CD226 p.Gln115Lys

c.343C>A · rs763900514 · VCV2298605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0868 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0868	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -7.38	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 -5.4
Regional constraint	o/e 0.96	unconstrained · MANE · 83 kb · p 0.44 · regional, not allelic
Overall
CADD	0.332	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 8.48e-05% European (non-Finnish) · 1/1,179,928 alleles

Overall 6.84e-05% 1/1,461,802 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: CD226
Protein: p.Gln115Lys
Coding: c.343C>A
MANE Select: NM_001303618
dbSNP: rs763900514
Type: single nucleotide variant
Location: chr18:69946773 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.75 · 2 PDB
Residue 115: the ig-like c2-type 1 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-gln115lys (accessed [today's date]).

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