Is CROT p.Pro115Leu (c.344C>T) pathogenic?

CROT p.Pro115Leu (c.344C>T) is classified Uncertain significance in CROT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely benign (0.1351); Absent from gnomAD v4.1.

How common is CROT p.Pro115Leu (c.344C>T) in the general population?

CROT p.Pro115Leu (c.344C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CROT p.Pro115Leu (c.344C>T)?

AlphaMissense predicts likely benign (score 0.1351) — an in-silico prediction, not a clinical call.

CROT p.Pro115Leu

c.344C>T · VCV4656781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1351 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1351	likely benign
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -5.67	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 50 kb · p 0.53 · regional, not allelic
Overall
CADD	26.5	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

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.Pro115Leu
Coding: c.344C>T
MANE Select: NM_021151
Type: single nucleotide variant
Location: chr7:87361493 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.22

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

Similar variants

CROT c.116-1631C>T Uncertain significance ★ same type
CROT c.116-1651G>A Uncertain significance ★ same type
CROT c.116-1663C>A Uncertain significance ★ same type
CROT c.116-1686C>G Uncertain significance ★ same type
CROT p.Ala104Val Uncertain significance ★ ⚠ same type
CROT p.Arg12Gln Uncertain significance ★ ⚠ same type
CROT p.Arg160Gln Uncertain significance ★ ⚠ same type
CROT p.Arg389Gly 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/crot-p-pro115leu (accessed [today's date]).

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