Is CATSPER2 p.Ser240Arg (c.720C>A) pathogenic?

CATSPER2 p.Ser240Arg (c.720C>A) is classified Uncertain significance in CATSPER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely pathogenic (0.7088); Very rare (popmax 0.00223%, eas).

How common is CATSPER2 p.Ser240Arg (c.720C>A) in the general population?

CATSPER2 p.Ser240Arg (c.720C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CATSPER2 p.Ser240Arg (c.720C>A)?

AlphaMissense predicts likely pathogenic (score 0.7088) — an in-silico prediction, not a clinical call.

CATSPER2 p.Ser240Arg

c.720C>A · VCV3485416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7088	likely pathogenic · top 10% in CATSPER2
REVEL	0.72	pathogenic-leaning
SaProt	LLR -9.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.74	GERP -0.6, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 3,470 bp · p 0.033 · regional, not allelic
Overall
CADD	22.5	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 0.00223% East Asian · 1/44,780 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,460,238 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,780
European (non-Finnish)	0.000339%	294,734

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: CATSPER2
Protein: p.Ser240Arg
Coding: c.720C>A
MANE Select: NM_172095
Type: single nucleotide variant
Location: chr15:43639026 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.83

Full CATSPER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CATSPER2 p.Arg498Ter Uncertain significance ★★ same type
CATSPER2 c.1178+188A>G Benign ★★ same type
CATSPER2 c.1179-15A>C Benign ★★ same type
CATSPER2 c.1179-2A>T Benign ★★ same type
CATSPER2 c.1179-3A>C Benign ★★ same type
CATSPER2 c.1179-8T>C Benign ★★ same type
CATSPER2 c.1397-121C>T Benign ★★ same type
CATSPER2 c.1397-29G>A Benign ★★ 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/catsper2-p-ser240arg (accessed [today's date]).

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