Is CAPN12 p.Ala478= (c.1434C>T) pathogenic?

CAPN12 p.Ala478= (c.1434C>T) is classified Benign in CAPN12 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Low-frequency (popmax 3.45%, afr); Associated with CAPN12-related disorder.

What condition is associated with CAPN12 p.Ala478= (c.1434C>T)?

CAPN12 p.Ala478= (c.1434C>T) is associated with CAPN12-related disorder (ClinVar).

How common is CAPN12 p.Ala478= (c.1434C>T) in the general population?

CAPN12 p.Ala478= (c.1434C>T) is low-frequency (popmax 3.45%, afr) (gnomAD).

CAPN12 p.Ala478=

c.1434C>T · rs574197181 · VCV3053830

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.45%, afr)

Conditions

CAPN12-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Pangolin	Δ0.33	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -2.1	GERP -2.9
Overall
CADD	15.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.45% African / African-American · 2,326/67,508 alleles

Filtering AF 3.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.28%

Overall 0.176% 2,586/1,465,884 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.45%	29
Admixed American	0.231%	434
Remaining individualsnot grpmax-eligible	0.228%	439
Middle Eastern	0.0473%	2,112
South Asian	0.00551%	18,154
European (non-Finnish)	0.00304%	32,876

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.Ala478=
Coding: c.1434C>T
MANE Select: NM_144691
dbSNP: rs574197181
Type: single nucleotide variant
Location: chr19:38736259 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 478: 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 p.Ala478Gly Benign ⚠ same residue
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

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-ala478 (accessed [today's date]).

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