Is CAPN1 p.Asp673fs (c.2017_2023del) pathogenic?

CAPN1 p.Asp673fs (c.20172023del) is classified Pathogenic in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Very rare (popmax 0.000254%, nfe).

How common is CAPN1 p.Asp673fs (c.2017_2023del) in the general population?

CAPN1 p.Asp673fs (c.2017_2023del) is very rare (popmax 0.000254%, nfe) (gnomAD).

CAPN1 p.Asp673fs

c.2017_2023del · VCV4703719

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 20 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,698 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,028 alleles · very rare

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: CAPN1
Protein: p.Asp673fs
Coding: c.2017_2023del
MANE Select: NM_005186
Type: Deletion
Location: chr11:65210408 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 673: the 'domain iv' region

Full CAPN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN1 p.Arg377fs Pathogenic/Likely pathogenic ★★ same type
CAPN1 p.Gly208fs Pathogenic ★★ same type
CAPN1 c.843+114del Benign/Likely benign ★★ same type
CAPN1 p.Pro136fs Pathogenic ★ same type
CAPN1 p.Ser206fs Pathogenic ★ same type
CAPN1 p.Glu431_Arg433del Uncertain significance ★ same type
CAPN1 p.Val178_Phe186del Uncertain significance ★ same type
CAPN1 c.456+18del Benign ★ 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/capn1-p-asp673fs (accessed [today's date]).

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