Is CLRN1 p.Cys147fs (c.438del) pathogenic?

CLRN1 p.Cys147fs (c.438del) is classified Likely pathogenic in CLRN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Associated with Usher syndrome type 3.

What condition is associated with CLRN1 p.Cys147fs (c.438del)?

CLRN1 p.Cys147fs (c.438del) is associated with Usher syndrome type 3 (ClinVar).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CLRN1 p.Cys147fs

c.438del · VCV4816964

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Usher syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: CLRN1
Protein: p.Cys147fs
Coding: c.438del
MANE Select: NM_174878
Type: Deletion
Location: chr3:150928197 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.74

Full CLRN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CLRN1 p.Cys147Ser Uncertain significance ⚠ same residue
CLRN1 p.Phe193fs Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Val101fs Pathogenic ★★ same condition
CLRN1 p.Cys147Tyr Likely pathogenic ★ ⚠ same residue
CLRN1 p.Ile153_Leu154delinsMet Likely pathogenic ★ same condition
CLRN1 p.Phe155fs Likely pathogenic ★ same condition
CLRN1 p.Tyr63fs Pathogenic ★ same condition
CLRN1 p.Ala117fs Pathogenic same condition

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/clrn1-p-cys147fs (accessed [today's date]).

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