Is CAPN15 p.Ser859= (c.2577C>T) pathogenic?

CAPN15 p.Ser859= (c.2577C>T) is classified Likely benign in CAPN15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-23). Rare (popmax 0.276%, sas); Associated with CAPN15-related disorder.

What condition is associated with CAPN15 p.Ser859= (c.2577C>T)?

CAPN15 p.Ser859= (c.2577C>T) is associated with CAPN15-related disorder (ClinVar).

How common is CAPN15 p.Ser859= (c.2577C>T) in the general population?

CAPN15 p.Ser859= (c.2577C>T) is rare (popmax 0.276%, sas) (gnomAD).

CAPN15 p.Ser859=

c.2577C>T · rs75045595 · VCV3053063

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.276%, sas)

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 -5.1	GERP -3
Overall
CADD	1.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.276% South Asian · 249/90,242 alleles

Filtering AF 0.248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.237%

Overall 0.0344% 551/1,600,542 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.276%	362
European (non-Finnish)	0.024%	4,174
Middle Eastern	0.0165%	6,050
Remaining individualsnot grpmax-eligible	0.0161%	6,201
African / African-American	0.00535%	18,708
East Asian	0.00449%	22,264
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,428
Admixed American	0.00337%	29,649

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.Ser859=
Coding: c.2577C>T
MANE Select: NM_005632
dbSNP: rs75045595
Type: single nucleotide variant
Location: chr16:552370 (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-ser859 (accessed [today's date]).

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