Is CROT p.His560Arg (c.1679A>G) pathogenic?

CROT p.His560Arg (c.1679A>G) is classified Uncertain significance in CROT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.0718); Very rare (popmax 0.0011%, sas).

How common is CROT p.His560Arg (c.1679A>G) in the general population?

CROT p.His560Arg (c.1679A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CROT p.His560Arg (c.1679A>G)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

CROT p.His560Arg

c.1679A>G · VCV3497273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -3.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.9	GERP -0.68, phastCons 0.15
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.53 · regional, not allelic
Overall
CADD	16.95	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 0.0011% South Asian · 1/91,068 alleles

Overall 0.000124% 2/1,613,488 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,068
European (non-Finnish)	8.48e-05%	1,179,638

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: CROT
Protein: p.His560Arg
Coding: c.1679A>G
MANE Select: NM_000443 · reported on NM_021151
Type: single nucleotide variant
Location: chr7:87393028 (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-his560arg (accessed [today's date]).

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