Is CATIP p.Glu349Val (c.1046A>T) pathogenic?

CATIP p.Glu349Val (c.1046A>T) is classified Uncertain significance in CATIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: ambiguous (0.3851); Ultra-rare (popmax 0.0317%, amr).

How common is CATIP p.Glu349Val (c.1046A>T) in the general population?

CATIP p.Glu349Val (c.1046A>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CATIP p.Glu349Val (c.1046A>T)?

AlphaMissense predicts ambiguous (score 0.3851) — an in-silico prediction, not a clinical call.

CATIP p.Glu349Val

c.1046A>T · rs758001254 · VCV2397967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3851 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Computational evidence

Protein change
AlphaMissense	0.3851	ambiguous
REVEL	0.591	indeterminate
SaProt	LLR -10.83	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 11 kb · p 0.75 · regional, not allelic
Overall
CADD	24.7	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 0.0317% Admixed American · 19/59,994 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00143% 23/1,613,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
Remaining individualsnot grpmax-eligible	0.0016%	62,462
European (non-Finnish)	0.000254%	393,295

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: CATIP
Protein: p.Glu349Val
Coding: c.1046A>T
MANE Select: NM_198559
dbSNP: rs758001254
Type: single nucleotide variant
Location: chr2:218367846 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.37

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

Similar variants

CATIP p.Ala363Thr Uncertain significance ★★ ⚠ same type
CATIP p.Ser57Leu Uncertain significance ★★ ⚠ same type
CATIP p.Phe35Ile Likely pathogenic ★ ⚠ same type
CATIP p.Ala348Thr Uncertain significance ★ ⚠ same type
CATIP p.Arg187Gln Uncertain significance ★ ⚠ same type
CATIP p.Arg195Cys Uncertain significance ★ ⚠ same type
CATIP p.Arg311Gln Uncertain significance ★ ⚠ same type
CATIP p.Arg383Gly 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/catip-p-glu349val (accessed [today's date]).

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