Is CAPN12 p.Ala110= (c.330T>C) pathogenic?

CAPN12 p.Ala110= (c.330T>C) is classified Benign in CAPN12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-09-11). Common (popmax 84.8%, sas) — too common for a highly-penetrant pathogenic allele; Associated with CAPN12-related disorder.

What condition is associated with CAPN12 p.Ala110= (c.330T>C)?

CAPN12 p.Ala110= (c.330T>C) is associated with CAPN12-related disorder (ClinVar).

CAPN12 p.Ala110=

Q: How common is CAPN12 p.Ala110= (c.330T>C) in the general population?

CAPN12 p.Ala110= (c.330T>C) is common (popmax 84.8%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330T>C · rs936524 · VCV3060668

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 84.8%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

CAPN12-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.4
Overall
CADD	0.004	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 84.8% South Asian · 77,117/90,914 alleles

Filtering AF 84.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 84.1%

Overall 74.3% 1,196,337/1,611,136 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	88.3%	1
South Asiangrpmax	84.8%	1
European (non-Finnish)	75.8%	1
Middle Eastern	73.9%	1
Remaining individualsnot grpmax-eligible	73.5%	1
Finnishnot grpmax-eligible	72.8%	1
Ashkenazi Jewishnot grpmax-eligible	70.4%	1
East Asian	67.6%	1
Admixed American	62.1%	2
African / African-American	54.6%	2

Amish 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: CAPN12
Protein: p.Ala110=
Coding: c.330T>C
MANE Select: NM_144691
dbSNP: rs936524
Type: single nucleotide variant
Location: chr19:38742506 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 110: the calpain catalytic domain

Full CAPN12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN12-related disorder

Similar variants

CAPN12 c.1627-6C>A Uncertain significance ★ same condition
CAPN12 p.Gln626Ter Uncertain significance ★ same condition
CAPN12 p.Phe139Val Uncertain significance ★ ⚠ same condition
CAPN12 p.Trp363Arg Uncertain significance ⚠ same condition
CAPN12 c.1583+9C>T Likely benign same condition
CAPN12 c.1879-3C>T Likely benign same condition
CAPN12 c.561-7C>T Likely benign same condition
CAPN12 p.Ala409= Likely benign 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/capn12-p-ala110 (accessed [today's date]).

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