Is CLRN1 p.Tyr63fs (c.188_210del) pathogenic?

CLRN1 p.Tyr63fs (c.188210del) is classified Pathogenic in CLRN1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-15). Absent from gnomAD; Associated with Usher syndrome type 3.

What condition is associated with CLRN1 p.Tyr63fs (c.188_210del)?

CLRN1 p.Tyr63fs (c.188_210del) is associated with Usher syndrome type 3 (ClinVar).

How common is CLRN1 p.Tyr63fs (c.188_210del) in the general population?

CLRN1 p.Tyr63fs (c.188_210del) is absent from gnomAD (gnomAD).

How is Usher syndrome inherited?

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

CLRN1 p.Tyr63fs

c.188_210del · rs1553776036 · VCV4398

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.3	GERP -0.14

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: CLRN1
Protein: p.Tyr63fs
Coding: c.188_210del
MANE Select: NM_174878
dbSNP: rs1553776036
Type: Deletion
Location: chr3:150972499 (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.Tyr63Ter Pathogenic ★★ same residue
CLRN1 p.Phe193fs Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Tyr63Ser Pathogenic ★★ same residue
CLRN1 p.Val101fs Pathogenic ★★ same condition
CLRN1 p.Cys147fs Likely pathogenic ★ same condition
CLRN1 p.Ile153_Leu154delinsMet Likely pathogenic ★ same condition
CLRN1 p.Phe155fs Likely pathogenic ★ same condition
CLRN1 p.Tyr63= Likely benign ★ same residue

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-tyr63fs (accessed [today's date]).

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