Is ATRAID p.Cys171Arg (c.511T>C) pathogenic?

ATRAID p.Cys171Arg (c.511T>C) is classified Uncertain significance in ATRAID (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely pathogenic (0.9211); Very rare (popmax 8.48e-05%, nfe).

How common is ATRAID p.Cys171Arg (c.511T>C) in the general population?

ATRAID p.Cys171Arg (c.511T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ATRAID p.Cys171Arg (c.511T>C)?

AlphaMissense predicts likely pathogenic (score 0.9211) — an in-silico prediction, not a clinical call.

ATRAID p.Cys171Arg

c.511T>C · rs201778106 · VCV3132113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9211 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9211	likely pathogenic · top 4% in ATRAID
REVEL	0.821	moderately pathogenic-leaning
SaProt	LLR -14.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,576 bp · p 0.19 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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) · 1/1,179,870 alleles

Overall 6.84e-05% 1/1,461,706 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: ATRAID
Protein: p.Cys171Arg
Coding: c.511T>C
MANE Select: NM_001170795
dbSNP: rs201778106
Type: single nucleotide variant
Location: chr2:27216546 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.31
Residue 171: a disulfide bond; the egf-like domain

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

Similar variants

ATRAID p.Cys171Ser Uncertain significance ★ ⚠ same residue
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

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-cys171arg (accessed [today's date]).

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