Is CAPN10 p.Pro9Ser (c.25C>T) pathogenic?

CAPN10 p.Pro9Ser (c.25C>T) is classified Uncertain significance in CAPN10 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0847); Very rare (popmax 0.000453%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAPN10 p.Pro9Ser (c.25C>T)?

CAPN10 p.Pro9Ser (c.25C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN10 p.Pro9Ser (c.25C>T) in the general population?

CAPN10 p.Pro9Ser (c.25C>T) is very rare (popmax 0.000453%, nfe) (gnomAD).

What do computational predictors say about CAPN10 p.Pro9Ser (c.25C>T)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

CAPN10 p.Pro9Ser

c.25C>T · rs2093071654 · VCV2335548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000453%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.256	benign-leaning
SaProt	LLR -7.10	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 0.89	GERP 0.9, phastCons 0.79
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.013 · regional, not allelic
Overall
CADD	19.08	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 0.000453% European (non-Finnish) · 5/1,103,736 alleles

Filtering AF 0.000133% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.7e-05%

Overall 0.000384% 5/1,300,406 alleles · very rare

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: CAPN10
Protein: p.Pro9Ser
Coding: c.25C>T
MANE Select: NM_023083
dbSNP: rs2093071654
Type: single nucleotide variant
Location: chr2:240586936 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91

Full CAPN10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAPN10 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
CAPN10 p.Gly526Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Pro46Ser Uncertain significance ★★ ⚠ same condition
CAPN10 p.Thr339Met Uncertain significance ★★ ⚠ same condition
CAPN10 p.Ala156Thr Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala252Val Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala341Thr Uncertain significance ★ ⚠ same condition
CAPN10 p.Ala389Val Uncertain significance ★ ⚠ same condition

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/capn10-p-pro9ser (accessed [today's date]).

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