Is CAPN5 p.Asp368fs (c.1102del) pathogenic?

CAPN5 p.Asp368fs (c.1102del) is classified Uncertain significance in CAPN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). Ultra-rare (popmax 0.01%, amr).

How common is CAPN5 p.Asp368fs (c.1102del) in the general population?

CAPN5 p.Asp368fs (c.1102del) is ultra-rare (popmax 0.01%, amr) (gnomAD).

CAPN5 p.Asp368fs

c.1102del · rs1467548403 · VCV1498949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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 8 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 0.8, phastCons 1
Overall
CADD	24.0	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

Grpmax group 0.01% Admixed American · 6/59,952 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,614 alleles · ultra-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: CAPN5
Protein: p.Asp368fs
Coding: c.1102del
MANE Select: NM_004055
dbSNP: rs1467548403
Type: Deletion
Location: chr11:77118286 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 91.71 · 1 PDB
Residue 368: the 'domain iii' region

Full CAPN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN5 p.Asp368His Uncertain significance ★ ⚠ same residue
CAPN5 p.Leu31fs Uncertain significance ★★ same type
CAPN5 p.Ser634_Ter641del Uncertain significance ★★ same type
CAPN5 p.Tyr41del Uncertain significance ★★ same type
CAPN5 c.971+11_971+12del Likely benign ★★ same type
CAPN5 c.165+5del Uncertain significance ★ same type
CAPN5 p.Arg62fs Uncertain significance ★ same type
CAPN5 p.Asp462fs Uncertain significance ★ 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/capn5-p-asp368fs (accessed [today's date]).

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