Is CAPNS2 p.Asp231Val (c.692A>T) pathogenic?

CAPNS2 p.Asp231Val (c.692A>T) is classified Uncertain significance in CAPNS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: ambiguous (0.4117); Absent from gnomAD v4.1.

How common is CAPNS2 p.Asp231Val (c.692A>T) in the general population?

CAPNS2 p.Asp231Val (c.692A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPNS2 p.Asp231Val (c.692A>T)?

AlphaMissense predicts ambiguous (score 0.4117) — an in-silico prediction, not a clinical call.

CAPNS2 p.Asp231Val

c.692A>T · rs1277890504 · VCV2292500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4117 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4117	ambiguous
REVEL	0.096	moderately benign-leaning
SaProt	LLR -11.73	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP -2.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 743 bp · p 0.19 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAPNS2
Protein: p.Asp231Val
Coding: c.692A>T
MANE Select: NM_032330
dbSNP: rs1277890504
Type: single nucleotide variant
Location: chr16:55567448 (GRCh38)
Gene constraint: LOEUF 1.114 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.67
Residue 231: the ef-hand 4 domain

Full CAPNS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPNS2 p.Ala18Val Uncertain significance ★ ⚠ same type
CAPNS2 p.Arg125Gln Uncertain significance ★ ⚠ same type
CAPNS2 p.Arg196Trp Uncertain significance ★ ⚠ same type
CAPNS2 p.Arg215His Uncertain significance ★ ⚠ same type
CAPNS2 p.Arg221His Uncertain significance ★ same type
CAPNS2 p.Arg221Leu Uncertain significance ★ ⚠ same type
CAPNS2 p.Arg82Trp Uncertain significance ★ same type
CAPNS2 p.Asp132Gly 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/capns2-p-asp231val (accessed [today's date]).

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