Is CROT p.Ala577Gly (c.1730C>G) pathogenic?

CROT p.Ala577Gly (c.1730C>G) is classified Uncertain significance in CROT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely benign (0.1835); Absent from gnomAD v4.1.

How common is CROT p.Ala577Gly (c.1730C>G) in the general population?

CROT p.Ala577Gly (c.1730C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CROT p.Ala577Gly (c.1730C>G)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

CROT p.Ala577Gly

c.1730C>G · VCV3269608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -5.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP 1.9, phastCons 0.61
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.53 · regional, not allelic
Overall
CADD	19.09	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CROT
Protein: p.Ala577Gly
Coding: c.1730C>G
MANE Select: NM_000443 · reported on NM_021151
Type: single nucleotide variant
Location: chr7:87398535 (GRCh38)

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

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/crot-p-ala577gly (accessed [today's date]).

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