Is ATRAID p.Arg223Gly (c.667C>G) pathogenic?

ATRAID p.Arg223Gly (c.667C>G) is classified Uncertain significance in ATRAID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.4431); Absent from gnomAD v4.1.

How common is ATRAID p.Arg223Gly (c.667C>G) in the general population?

ATRAID p.Arg223Gly (c.667C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRAID p.Arg223Gly (c.667C>G)?

AlphaMissense predicts ambiguous (score 0.4431) — an in-silico prediction, not a clinical call.

ATRAID p.Arg223Gly

c.667C>G · VCV3463719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4431 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4431	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -8.01	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,576 bp · p 0.19 · regional, not allelic
Overall
CADD	28.7	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

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: ATRAID
Protein: p.Arg223Gly
Coding: c.667C>G
MANE Select: NM_001170795
Type: single nucleotide variant
Location: chr2:27216925 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31

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

Similar variants

ATRAID c.-117C>A Uncertain significance ★ same type
ATRAID c.-123A>C Uncertain significance ★ same type
ATRAID c.-155G>A Uncertain significance ★ same type
ATRAID c.-161A>G Uncertain significance ★ same type
ATRAID c.-24A>T Uncertain significance ★ same type
ATRAID c.-38C>T Uncertain significance ★ same type
ATRAID c.-44C>G Uncertain significance ★ same type
ATRAID c.-71G>A 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/atraid-p-arg223gly (accessed [today's date]).

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