Is CAPN15 p.Glu104= (c.312A>G) pathogenic?

CAPN15 p.Glu104= (c.312A>G) is classified Benign in CAPN15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-12). Low-frequency (popmax 1.44%, afr); Associated with CAPN15-related disorder.

What condition is associated with CAPN15 p.Glu104= (c.312A>G)?

CAPN15 p.Glu104= (c.312A>G) is associated with CAPN15-related disorder (ClinVar).

How common is CAPN15 p.Glu104= (c.312A>G) in the general population?

CAPN15 p.Glu104= (c.312A>G) is low-frequency (popmax 1.44%, afr) (gnomAD).

CAPN15 p.Glu104=

c.312A>G · rs74003979 · VCV3040222

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, afr)

Conditions

CAPN15-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 -0.083	GERP 0.15, phastCons 0.001
Overall
CADD	0.777	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.44% African / African-American · 1,070/74,162 alleles

Filtering AF 1.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.34%

Overall 0.0748% 1,159/1,550,316 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.44%	69
Remaining individualsnot grpmax-eligible	0.0782%	1,279
Admixed American	0.0608%	1,645
Middle Eastern	0.017%	5,866
South Asian	0.00364%	27,453
European (non-Finnish)	0.000435%	230,142

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: CAPN15
Protein: p.Glu104=
Coding: c.312A>G
MANE Select: NM_005632
dbSNP: rs74003979
Type: single nucleotide variant
Location: chr16:547150 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.65

Full CAPN15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CAPN15-related disorder

Similar variants

CAPN15 p.Pro494Ser Uncertain significance ★ ⚠ same condition
CAPN15 p.Ser613Leu Conflicting classifications of pathogenicity ★ ⚠ same condition
CAPN15 p.Thr950Ala Uncertain significance ⚠ same condition
CAPN15 p.Ala559= Likely benign same condition
CAPN15 p.Ala817= Likely benign same condition
CAPN15 p.Arg428Gln Likely benign same condition
CAPN15 p.Asn745= Likely benign same condition
CAPN15 p.Asp590= 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/capn15-p-glu104 (accessed [today's date]).

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