Is CLRN1 p.Pro134Arg (c.401C>G) pathogenic?

CLRN1 p.Pro134Arg (c.401C>G) is classified Uncertain significance in CLRN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-01-01). AlphaMissense: likely benign (0.299); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CLRN1 p.Pro134Arg (c.401C>G)?

CLRN1 p.Pro134Arg (c.401C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is CLRN1 p.Pro134Arg (c.401C>G) in the general population?

CLRN1 p.Pro134Arg (c.401C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLRN1 p.Pro134Arg (c.401C>G)?

AlphaMissense predicts likely benign (score 0.299) — an in-silico prediction, not a clinical call.

CLRN1 p.Pro134Arg

c.401C>G · VCV3250303

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.299 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.299	likely benign
REVEL	0.936	strongly pathogenic-leaning
SaProt	LLR -9.52	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 45 kb · p 0.044 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLRN1
Protein: p.Pro134Arg
Coding: c.401C>G
MANE Select: NM_174878
Type: single nucleotide variant
Location: chr3:150941614 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLRN1 p.Pro134Leu Uncertain significance ★★ ⚠ same residue
CLRN1 p.Pro134Ser Uncertain significance ★★ ⚠ same residue
CLRN1 p.Pro134Ala Uncertain significance ★ ⚠ same residue
CLRN1 p.Pro134= Likely benign ★ same residue
CLRN1 p.Asn202Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CLRN1 c.433+1083A>G Uncertain significance ★★ same condition
CLRN1 p.Gln73Arg Uncertain significance ★★ ⚠ same condition
CLRN1 p.Gly136Glu Uncertain significance ★★ ⚠ 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-pro134arg (accessed [today's date]).

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