Is CAT p.Leu299Phe (c.895C>T) pathogenic?

CAT p.Leu299Phe (c.895C>T) is classified Uncertain significance in CAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: likely pathogenic (0.9398); Absent from gnomAD v4.1.

How common is CAT p.Leu299Phe (c.895C>T) in the general population?

CAT p.Leu299Phe (c.895C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAT p.Leu299Phe (c.895C>T)?

AlphaMissense predicts likely pathogenic (score 0.9398) — an in-silico prediction, not a clinical call.

CAT p.Leu299Phe

c.895C>T · rs1365498884 · VCV2550790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9398 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9398	likely pathogenic
REVEL	0.528	indeterminate
SaProt	LLR -13.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -3.7, phastCons 0.003
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.47 · regional, not allelic
Overall
CADD	13.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CAT
Protein: p.Leu299Phe
Coding: c.895C>T
MANE Select: NM_001752
dbSNP: rs1365498884
Type: single nucleotide variant
Location: chr11:34456194 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.97 · 17 PDB

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

Similar variants

CAT c.239-5G>A Benign/Likely benign ★★ same type
CAT p.Arg189Cys Benign/Likely benign ★★ same type
CAT p.Asn439= Likely benign ★★ same type
CAT p.Gly390Asp Benign ★★ same type
CAT p.His209Tyr Likely benign ★★ same type
CAT p.His492= Benign/Likely benign ★★ same type
CAT p.Ile109= Benign/Likely benign ★★ same type
CAT p.Phe185= Benign/Likely benign ★★ 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/cat-p-leu299phe (accessed [today's date]).

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