Is CATIP p.Ser92Arg (c.276C>G) pathogenic?

CATIP p.Ser92Arg (c.276C>G) is classified Uncertain significance in CATIP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely pathogenic (0.8024); Very rare (popmax 8.47e-05%, nfe).

How common is CATIP p.Ser92Arg (c.276C>G) in the general population?

CATIP p.Ser92Arg (c.276C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CATIP p.Ser92Arg (c.276C>G)?

AlphaMissense predicts likely pathogenic (score 0.8024) — an in-silico prediction, not a clinical call.

CATIP p.Ser92Arg

c.276C>G · rs1200960981 · VCV3137742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8024 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8024	likely pathogenic · top 6% in CATIP
REVEL	0.474	indeterminate
SaProt	LLR -13.11	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 2.6	GERP 0.85, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 11 kb · p 0.75 · regional, not allelic
Overall
CADD	21.6	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,798 alleles · very rare

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.Ser92Arg
Coding: c.276C>G
MANE Select: NM_198559
dbSNP: rs1200960981
Type: single nucleotide variant
Location: chr2:218357691 (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-ser92arg (accessed [today's date]).

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