Is CATSPERB p.Pro342Arg (c.1025C>G) pathogenic?

CATSPERB p.Pro342Arg (c.1025C>G) is classified Uncertain significance in CATSPERB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.3421); Very rare (popmax 0.000255%, nfe).

How common is CATSPERB p.Pro342Arg (c.1025C>G) in the general population?

CATSPERB p.Pro342Arg (c.1025C>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CATSPERB p.Pro342Arg (c.1025C>G)?

AlphaMissense predicts ambiguous (score 0.3421) — an in-silico prediction, not a clinical call.

CATSPERB p.Pro342Arg

c.1025C>G · VCV3995844

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3421	ambiguous
REVEL	0.238	benign-leaning
SaProt	LLR -9.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.20	acceptor gain, 46 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 149 kb · p 1.3e-06 · regional, not allelic
Overall
CADD	23.5	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 0.000255% European (non-Finnish) · 3/1,174,700 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000189% 3/1,590,470 alleles · very rare exomes 2/1,438,554 · genomes 1/151,916 · joint denominator

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: CATSPERB
Protein: p.Pro342Arg
Coding: c.1025C>G
MANE Select: NM_024764
Type: single nucleotide variant
Location: chr14:91672970 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.99

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

Similar variants

CATSPERB p.Ala127Val Uncertain significance ★ ⚠ same type
CATSPERB p.Ala190Asp Uncertain significance ★ ⚠ same type
CATSPERB p.Ala304Val Uncertain significance ★ ⚠ same type
CATSPERB p.Ala444Asp Uncertain significance ★ ⚠ same type
CATSPERB p.Ala444Thr Uncertain significance ★ ⚠ same type
CATSPERB p.Ala462Gly Uncertain significance ★ ⚠ same type
CATSPERB p.Ala519Thr Uncertain significance ★ ⚠ same type
CATSPERB p.Ala681Thr 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/catsperb-p-pro342arg (accessed [today's date]).

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