Is CRAT p.Arg615Leu (c.1844G>T) pathogenic?

CRAT p.Arg615Leu (c.1844G>T) is classified Benign in CRAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-04). AlphaMissense: ambiguous (0.4342); Low-frequency (popmax 1.04%, sas).

How common is CRAT p.Arg615Leu (c.1844G>T) in the general population?

CRAT p.Arg615Leu (c.1844G>T) is low-frequency (popmax 1.04%, sas) (gnomAD).

What do computational predictors say about CRAT p.Arg615Leu (c.1844G>T)?

AlphaMissense predicts ambiguous (score 0.4342) — an in-silico prediction, not a clinical call.

CRAT p.Arg615Leu

c.1844G>T · rs149016840 · VCV1598787

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4342 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.04%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4342	ambiguous
REVEL	0.695	pathogenic-leaning
SaProt	LLR -12.12	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.69, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 0.00046 · regional, not allelic
Overall
CADD	26.8	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 1.04% South Asian · 946/91,080 alleles

Filtering AF 0.984% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.962%

Overall 0.0688% 1,110/1,612,816 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.04%	96
Middle Eastern	0.233%	428
Remaining individualsnot grpmax-eligible	0.08%	1,250
European (non-Finnish)	0.00797%	12,553
East Asian	0.00446%	22,442
Admixed American	0.00333%	30,012
African / African-American	0.00267%	37,522

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.Arg615Leu
Coding: c.1844G>T
MANE Select: NM_000755
dbSNP: rs149016840
Type: single nucleotide variant
Location: chr9:129095434 (GRCh38)
Gene constraint: LOEUF 1.111 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.75 · 3 PDB
Residue 615: an α-helix

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

Similar variants

CRAT p.Arg615Cys Uncertain significance ★★ ⚠ same residue
CRAT p.Arg615His 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

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-arg615leu (accessed [today's date]).

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