Is CLCN1 p.Asp429fs (c.1287del) pathogenic?

CLCN1 p.Asp429fs (c.1287del) is classified Pathogenic in CLCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-24). Absent from gnomAD.

How common is CLCN1 p.Asp429fs (c.1287del) in the general population?

CLCN1 p.Asp429fs (c.1287del) is absent from gnomAD (gnomAD).

CLCN1 p.Asp429fs

c.1287del · rs2116855176 · VCV1322087

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 12 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 3.5, 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: CLCN1
Protein: p.Asp429fs
Coding: c.1287del
MANE Select: NM_000083
dbSNP: rs2116855176
Type: Deletion
Location: chr7:143332759 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.34 · 9 PDB

Full CLCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCN1 p.Asp429Gly Uncertain significance ★ ⚠ same residue
CLCN1 c.434-1_437del Pathogenic/Likely pathogenic ★★ same type
CLCN1 p.Ala350fs Pathogenic/Likely pathogenic ★★ same type
CLCN1 p.Gln675fs Pathogenic ★★ same type
CLCN1 p.Glu624fs Pathogenic/Likely pathogenic ★★ same type
CLCN1 p.Glu656fs Pathogenic/Likely pathogenic ★★ same type
CLCN1 p.Gly11fs Pathogenic/Likely pathogenic ★★ same type
CLCN1 p.Gly41fs Pathogenic/Likely 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/clcn1-p-asp429fs (accessed [today's date]).

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