Is CRAT p.Arg90Gln (c.269G>A) pathogenic?

CRAT p.Arg90Gln (c.269G>A) is classified Uncertain significance in CRAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). AlphaMissense: likely benign (0.3143); Ultra-rare (popmax 0.0439%, sas).

How common is CRAT p.Arg90Gln (c.269G>A) in the general population?

CRAT p.Arg90Gln (c.269G>A) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

What do computational predictors say about CRAT p.Arg90Gln (c.269G>A)?

AlphaMissense predicts likely benign (score 0.3143) — an in-silico prediction, not a clinical call.

CRAT p.Arg90Gln

c.269G>A · rs374627309 · VCV1473271

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3143 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3143	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -9.73	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.00046 · regional, not allelic
Overall
CADD	29.6	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 0.0439% South Asian · 40/91,086 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00409% 66/1,612,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Finnishnot grpmax-eligible	0.00478%	20,933
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00267%	37,450
European (non-Finnish)	0.00161%	62,107

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: CRAT
Protein: p.Arg90Gln
Coding: c.269G>A
MANE Select: NM_000755
dbSNP: rs374627309
Type: single nucleotide variant
Location: chr9:129107836 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 90: an α-helix

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

Similar variants

CRAT p.Ala260Pro Uncertain significance ★★ ⚠ same type
CRAT p.Ala262Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala544Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala546Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala596Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala596Val Uncertain significance ★★ ⚠ same type
CRAT p.Ala600Thr Uncertain significance ★★ ⚠ same type
CRAT p.Ala604Val 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/crat-p-arg90gln (accessed [today's date]).

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