Is CATIP p.Asp142His (c.424G>C) pathogenic?

CATIP p.Asp142His (c.424G>C) is classified Uncertain significance in CATIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.1403); Absent from gnomAD v4.1.

How common is CATIP p.Asp142His (c.424G>C) in the general population?

CATIP p.Asp142His (c.424G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CATIP p.Asp142His (c.424G>C)?

AlphaMissense predicts likely benign (score 0.1403) — an in-silico prediction, not a clinical call.

CATIP p.Asp142His

c.424G>C · rs1405756833 · VCV2245777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1403 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1403	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP -0.35, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 11 kb · p 0.75 · regional, not allelic
Overall
CADD	20.7	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

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: CATIP
Protein: p.Asp142His
Coding: c.424G>C
MANE Select: NM_198559
dbSNP: rs1405756833
Type: single nucleotide variant
Location: chr2:218360621 (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-asp142his (accessed [today's date]).

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