Is CAPN10 p.Cys50Arg (c.148T>C) pathogenic?

CAPN10 p.Cys50Arg (c.148T>C) is classified Uncertain significance in CAPN10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-12). AlphaMissense: ambiguous (0.5302); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAPN10 p.Cys50Arg (c.148T>C)?

CAPN10 p.Cys50Arg (c.148T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CAPN10 p.Cys50Arg (c.148T>C) in the general population?

CAPN10 p.Cys50Arg (c.148T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CAPN10 p.Cys50Arg (c.148T>C)?

AlphaMissense predicts ambiguous (score 0.5302) — an in-silico prediction, not a clinical call.

CAPN10 p.Cys50Arg

c.148T>C · rs142471367 · VCV2219783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5302	ambiguous
REVEL	0.384	indeterminate
SaProt	LLR -12.93	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 0.96, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.013 · regional, not allelic
Overall
CADD	26.1	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 0.000821% 12/1,461,850 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,961
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,038

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys50Arg
Coding: c.148T>C
MANE Select: NM_023083
dbSNP: rs142471367
Type: single nucleotide variant
Location: chr2:240589349 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 50: the calpain catalytic domain

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-cys50arg (accessed [today's date]).

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