Is ATRAID p.Lys227Glu (c.679A>G) pathogenic?

ATRAID p.Lys227Glu (c.679A>G) is classified Uncertain significance in ATRAID (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely benign (0.2531); Absent from gnomAD v4.1.

How common is ATRAID p.Lys227Glu (c.679A>G) in the general population?

ATRAID p.Lys227Glu (c.679A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRAID p.Lys227Glu (c.679A>G)?

AlphaMissense predicts likely benign (score 0.2531) — an in-silico prediction, not a clinical call.

ATRAID p.Lys227Glu

c.679A>G · rs2465265988 · VCV2327813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2531 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2531	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,576 bp · p 0.19 · regional, not allelic
Overall
CADD	25.7	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: ATRAID
Protein: p.Lys227Glu
Coding: c.679A>G
MANE Select: NM_001170795
dbSNP: rs2465265988
Type: single nucleotide variant
Location: chr2:27216937 (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-lys227glu (accessed [today's date]).

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