Is CAT p.Gln255Arg (c.764A>G) pathogenic?

CAT p.Gln255Arg (c.764A>G) is classified Likely benign in CAT (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-24). AlphaMissense: likely benign (0.0772); Ultra-rare (popmax 0.0329%, mid); Associated with intellectual disability.

What condition is associated with CAT p.Gln255Arg (c.764A>G)?

CAT p.Gln255Arg (c.764A>G) is associated with intellectual disability (ClinVar).

How common is CAT p.Gln255Arg (c.764A>G) in the general population?

CAT p.Gln255Arg (c.764A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CAT p.Gln255Arg (c.764A>G)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CAT p.Gln255Arg

c.764A>G · VCV4074778

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -3.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.74, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.47 · regional, not allelic
Overall
CADD	19.81	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.024% 387/1,614,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.0308%	3,242
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
Admixed American	0.00667%	15,002
African / African-American	0.004%	24,976
Finnishnot grpmax-eligible	0.00156%	64,038

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: CAT
Protein: p.Gln255Arg
Coding: c.764A>G
MANE Select: NM_001752
Type: single nucleotide variant
Location: chr11:34456063 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.97 · 17 PDB
Residue 255: an α-helix

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAT c.1056+1G>C Conflicting classifications of pathogenicity ★ same condition
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

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-gln255arg (accessed [today's date]).

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