Is CD226 p.Arg283Lys (c.848G>A) pathogenic?

CD226 p.Arg283Lys (c.848G>A) is classified Likely benign in CD226 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely benign (0.0667); Ultra-rare (popmax 0.0168%, mid).

How common is CD226 p.Arg283Lys (c.848G>A) in the general population?

CD226 p.Arg283Lys (c.848G>A) is ultra-rare (popmax 0.0168%, mid) (gnomAD).

What do computational predictors say about CD226 p.Arg283Lys (c.848G>A)?

AlphaMissense predicts likely benign (score 0.0667) — an in-silico prediction, not a clinical call.

CD226 p.Arg283Lys

c.848G>A · rs533971919 · VCV2544875

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0667 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0667	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.37	GERP -2
Regional constraint	o/e 0.96	unconstrained · MANE · 83 kb · p 0.44 · regional, not allelic
Overall
CADD	1.226	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 0.0168% Middle Eastern · 1/5,946 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.000652% 10/1,533,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0168%	5,946
South Asian	0.00671%	14,907
East Asian	0.0045%	22,231
European (non-Finnish)	9.03e-05%	1,107,394

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.Arg283Lys
Coding: c.848G>A
MANE Select: NM_001303618
dbSNP: rs533971919
Type: single nucleotide variant
Location: chr18:69867394 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.75 · 2 PDB

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-arg283lys (accessed [today's date]).

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