Is CATSPER2 p.Glu8Val (c.23A>T) pathogenic?

CATSPER2 p.Glu8Val (c.23A>T) is classified Uncertain significance in CATSPER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.114); Absent from gnomAD v4.1.

How common is CATSPER2 p.Glu8Val (c.23A>T) in the general population?

CATSPER2 p.Glu8Val (c.23A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CATSPER2 p.Glu8Val (c.23A>T)?

AlphaMissense predicts likely benign (score 0.114) — an in-silico prediction, not a clinical call.

CATSPER2 p.Glu8Val

c.23A>T · VCV3995819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.114 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,584)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.114	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.002	GERP -2.7, phastCons 0.006
Regional constraint	o/e 1.03	unconstrained · MANE · 7,638 bp · p 0.67 · regional, not allelic
Overall
CADD	12.07	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

No allele count reported in gnomAD v4.1 (AN 1,613,584). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CATSPER2
Protein: p.Glu8Val
Coding: c.23A>T
MANE Select: NM_172095
Type: single nucleotide variant
Location: chr15:43648039 (GRCh38)
Gene constraint: LOEUF 1.047 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.83
Residue 8: 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-glu8val (accessed [today's date]).

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