Is CAPN12 p.Phe453= (c.1359C>T) pathogenic?

CAPN12 p.Phe453= (c.1359C>T) is classified Likely benign in CAPN12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-02). Ultra-rare (popmax 0.0847%, sas); Associated with CAPN12-related disorder.

What condition is associated with CAPN12 p.Phe453= (c.1359C>T)?

CAPN12 p.Phe453= (c.1359C>T) is associated with CAPN12-related disorder (ClinVar).

How common is CAPN12 p.Phe453= (c.1359C>T) in the general population?

CAPN12 p.Phe453= (c.1359C>T) is ultra-rare (popmax 0.0847%, sas) (gnomAD).

CAPN12 p.Phe453=

c.1359C>T · rs562501812 · VCV3043505

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, sas)

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 5.4	GERP -0.96, phastCons 1
Overall
CADD	13.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0847% South Asian · 71/83,860 alleles

Filtering AF 0.0688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.063%

Overall 0.00498% 77/1,546,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0847%	1,181
Remaining individualsnot grpmax-eligible	0.00668%	14,969
European (non-Finnish)	0.000175%	573,026

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.Phe453=
Coding: c.1359C>T
MANE Select: NM_144691
dbSNP: rs562501812
Type: single nucleotide variant
Location: chr19:38737159 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 453: the 'domain iii' region

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.Ala110= 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-phe453 (accessed [today's date]).

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