CAPN3 p.Gln653Ter
c.1957C>T · rs886042927 · VCV284707
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 17 of 24 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.22 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.7, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CAPN3
- Protein
- p.Gln653Ter
- Coding
- c.1957C>T
- MANE Select
- NM_000070
- dbSNP
- rs886042927
- Type
- single nucleotide variant
- Location
- chr15:42409345 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.18 · 5 PDB
- Residue 653
- the 'domain iv' region; the ef-hand 1 domain
Similar variants
- CAPN3 c.1115+5G>C Pathogenic ★★★ same type
- CAPN3 c.1194-2A>G Pathogenic ★★★ same type
- CAPN3 c.1194-9A>G Pathogenic ★★★ same type
- CAPN3 c.1746-20C>G Pathogenic ★★★ same type
- CAPN3 c.1993-1G>A Pathogenic ★★★ same type
- CAPN3 c.499-1G>A Pathogenic ★★★ same type
- CAPN3 p.Ala702Val Pathogenic ★★★ same type
- CAPN3 p.Ala798Glu Pathogenic ★★★ ⚠ same type
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/capn3-p-gln653ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown