Is CRAT p.Ala624Pro (c.1870G>C) pathogenic?

CRAT p.Ala624Pro (c.1870G>C) is classified Benign in CRAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.2027); Common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CRAT p.Ala624Pro (c.1870G>C)?

AlphaMissense predicts likely benign (score 0.2027) — an in-silico prediction, not a clinical call.

CRAT p.Ala624Pro

Q: How common is CRAT p.Ala624Pro (c.1870G>C) in the general population?

CRAT p.Ala624Pro (c.1870G>C) is common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1870G>C · rs17459086 · VCV1167631

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2027 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 15.1%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2027	likely benign
REVEL	0.374	indeterminate
SaProt	LLR -5.54	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 1.7	GERP 0.64, phastCons 0.93
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.00046 · regional, not allelic
Overall
CADD	22.5	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

Grpmax group 15.1% Admixed American · 9,084/59,996 alleles

Filtering AF 14.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.8%

Overall 1.87% 30,123/1,610,904 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	15.1%	7
East Asian	6.94%	14
Ashkenazi Jewishnot grpmax-eligible	3.94%	25
South Asian	3.84%	26
Remaining individualsnot grpmax-eligible	2.35%	42
Middle Eastern	1.98%	50
European (non-Finnish)	0.929%	108
African / African-American	0.9%	111
Finnishnot grpmax-eligible	0.0764%	1,309

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.Ala624Pro
Coding: c.1870G>C
MANE Select: NM_000755
dbSNP: rs17459086
Type: single nucleotide variant
Location: chr9:129095408 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 624: a UniProt-annotated variant site (in)

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

Similar variants

CRAT p.Ala624fs Uncertain significance ★ same residue
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

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-ala624pro (accessed [today's date]).

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