Is CATSPER1 p.Ala172Pro (c.514G>C) pathogenic?

CATSPER1 p.Ala172Pro (c.514G>C) is classified Uncertain significance in CATSPER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.0815); Very rare (popmax 0.00439%, sas).

How common is CATSPER1 p.Ala172Pro (c.514G>C) in the general population?

CATSPER1 p.Ala172Pro (c.514G>C) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about CATSPER1 p.Ala172Pro (c.514G>C)?

AlphaMissense predicts likely benign (score 0.0815) — an in-silico prediction, not a clinical call.

CATSPER1 p.Ala172Pro

c.514G>C · rs1178857660 · VCV2595919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0815 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0815	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -6.45	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 -15	GERP -3.2
Regional constraint	o/e 0.88	unconstrained · MANE · 9,486 bp · p 0.00012 · regional, not allelic
Overall
CADD	0.003	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 0.00439% South Asian · 4/91,014 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000342% 5/1,461,798 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,753
Remaining individualsnot grpmax-eligible	0.0016%	62,496

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: CATSPER1
Protein: p.Ala172Pro
Coding: c.514G>C
MANE Select: NM_053054
dbSNP: rs1178857660
Type: single nucleotide variant
Location: chr11:66025866 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.10
Residue 172: the 'disordered' region

Full CATSPER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CATSPER1 c.-8G>A Uncertain significance ★★ same type
CATSPER1 p.Arg297Gln Uncertain significance ★★ ⚠ same type
CATSPER1 p.Arg332Gln Uncertain significance ★★ ⚠ same type
CATSPER1 p.Arg558Trp Uncertain significance ★★ ⚠ same type
CATSPER1 p.Arg757Cys Uncertain significance ★★ ⚠ same type
CATSPER1 p.Gln324Glu Uncertain significance ★★ ⚠ same type
CATSPER1 p.Ile486Lys Uncertain significance ★★ ⚠ same type
CATSPER1 p.Ile583Ser 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/catsper1-p-ala172pro (accessed [today's date]).

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