Is CAPN1 p.Ser206fs (c.616_620del) pathogenic?

CAPN1 p.Ser206fs (c.616620del) is classified Pathogenic in CAPN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-23). Absent from gnomAD.

How common is CAPN1 p.Ser206fs (c.616_620del) in the general population?

CAPN1 p.Ser206fs (c.616_620del) is absent from gnomAD (gnomAD).

CAPN1 p.Ser206fs

c.616_620del · rs1948630635 · VCV987360

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 6 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAPN1
Protein: p.Ser206fs
Coding: c.616_620del
MANE Select: NM_005186
dbSNP: rs1948630635
Type: Deletion
Location: chr11:65186194 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.03 · 5 PDB
Residue 206: the calpain catalytic domain

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.Asp673fs Pathogenic ★ same type
CAPN1 p.Pro136fs 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-ser206fs (accessed [today's date]).

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