Is CATSPERG p.Pro88Ser (c.262C>T) pathogenic?

CATSPERG p.Pro88Ser (c.262C>T) is classified Uncertain significance in CATSPERG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.1542); Very rare (popmax 0.000174%, nfe).

How common is CATSPERG p.Pro88Ser (c.262C>T) in the general population?

CATSPERG p.Pro88Ser (c.262C>T) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about CATSPERG p.Pro88Ser (c.262C>T)?

AlphaMissense predicts likely benign (score 0.1542) — an in-silico prediction, not a clinical call.

CATSPERG p.Pro88Ser

c.262C>T · VCV3485480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1542 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1542	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -0.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.037	GERP -3.2
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 5e-07 · regional, not allelic
Overall
CADD	11.17	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

Grpmax group 0.000174% European (non-Finnish) · 2/1,147,082 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000143% 2/1,399,784 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: CATSPERG
Protein: p.Pro88Ser
Coding: c.262C>T
MANE Select: NM_021185
Type: single nucleotide variant
Location: chr19:38337496 (GRCh38)
Gene constraint: LOEUF 0.873 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.99
Residue 88: a disulfide bond

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

Similar variants

CATSPERG p.Ala1014Thr Uncertain significance ★ ⚠ same type
CATSPERG p.Ala1066Val Uncertain significance ★ ⚠ same type
CATSPERG p.Ala1086Thr Uncertain significance ★ ⚠ same type
CATSPERG p.Ala1118Thr Uncertain significance ★ ⚠ same type
CATSPERG p.Ala362Val Uncertain significance ★ ⚠ same type
CATSPERG p.Ala411Ser Uncertain significance ★ ⚠ same type
CATSPERG p.Ala411Thr Uncertain significance ★ ⚠ same type
CATSPERG p.Arg1065Gln 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/catsperg-p-pro88ser (accessed [today's date]).

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