Is CRAT p.Ala53= (c.159G>A) pathogenic?

CRAT p.Ala53= (c.159G>A) is classified Likely benign in CRAT (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-26). Rare (popmax 0.102%, sas).

How common is CRAT p.Ala53= (c.159G>A) in the general population?

CRAT p.Ala53= (c.159G>A) is rare (popmax 0.102%, sas) (gnomAD).

CRAT p.Ala53=

c.159G>A · rs149587791 · VCV2747927

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.207	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% South Asian · 93/90,932 alleles

Filtering AF 0.0855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0792%

Overall 0.0357% 575/1,608,930 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.219%	456
South Asiangrpmax	0.102%	978
Remaining individualsnot grpmax-eligible	0.0449%	2,230
European (non-Finnish)	0.0374%	2,675
African / African-American	0.00933%	10,722
Finnishnot grpmax-eligible	0.00336%	29,763
Admixed American	0.00334%	29,977

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala53=
Coding: c.159G>A
MANE Select: NM_000755
dbSNP: rs149587791
Type: single nucleotide variant
Location: chr9:129107946 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 53: 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-ala53 (accessed [today's date]).

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