Is CATSPER2 p.Val57Ile (c.169G>A) pathogenic?

CATSPER2 p.Val57Ile (c.169G>A) is classified Benign in CATSPER2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-05-09). AlphaMissense: likely benign (0.0942); Common (popmax 27.3%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CATSPER2 p.Val57Ile (c.169G>A)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

CATSPER2 p.Val57Ile

Q: How common is CATSPER2 p.Val57Ile (c.169G>A) in the general population?

CATSPER2 p.Val57Ile (c.169G>A) is common (popmax 27.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.169G>A · rs8042868 · VCV508570

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 27.3%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -4.93	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 0.42	GERP -0.57, phastCons 0.13
Regional constraint	o/e 1.03	unconstrained · MANE · 7,638 bp · p 0.67 · regional, not allelic
Overall
CADD	6.844	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 27.3% East Asian · 12,240/44,836 alleles

Filtering AF 26.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.7%

Overall 11.4% 183,868/1,612,710 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	27.3%	4
African / African-American	24.9%	4
Ashkenazi Jewishnot grpmax-eligible	18.3%	5
Admixed American	18.2%	5
South Asian	13.1%	8
Remaining individualsnot grpmax-eligible	12.6%	8
Middle Eastern	12.1%	8
Amishnot grpmax-eligible	10.6%	9
European (non-Finnish)	9.62%	10
Finnishnot grpmax-eligible	4.04%	25

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.Val57Ile
Coding: c.169G>A
MANE Select: NM_172095
dbSNP: rs8042868
Type: single nucleotide variant
Location: chr15:43647444 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.83
Residue 57: a UniProt-annotated variant site (in)

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-val57ile (accessed [today's date]).

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