Is CLRN1 p.Ser50Ala (c.148T>G) pathogenic?

CLRN1 p.Ser50Ala (c.148T>G) is classified Conflicting classifications of pathogenicity in CLRN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-24). AlphaMissense: likely benign (0.1695); Absent from gnomAD v4.1; Associated with CLRN1-related disorder.

What condition is associated with CLRN1 p.Ser50Ala (c.148T>G)?

CLRN1 p.Ser50Ala (c.148T>G) is associated with CLRN1-related disorder (ClinVar).

How common is CLRN1 p.Ser50Ala (c.148T>G) in the general population?

CLRN1 p.Ser50Ala (c.148T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLRN1 p.Ser50Ala (c.148T>G)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

CLRN1 p.Ser50Ala

c.148T>G · VCV3727422

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CLRN1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -8.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 45 kb · p 0.044 · regional, not allelic
Overall
CADD	23.9	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.Ser50Ala
Coding: c.148T>G
MANE Select: NM_174878
Type: single nucleotide variant
Location: chr3:150972561 (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

CLRN1-related disorder

Similar variants

CLRN1 p.Ser50_Gly51delinsCysProMet Conflicting classifications of pathogenicity ★ same residue
CLRN1 p.Ser50Ter Pathogenic ★★ same residue
CLRN1 c.254-2A>G Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.254-649T>G Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.433+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Ala123Asp Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Gln52Ter Pathogenic/Likely 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-ser50ala (accessed [today's date]).

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