Is CLRN1 p.Ser3Arg (c.9C>A) pathogenic?

CLRN1 p.Ser3Arg (c.9C>A) is classified Conflicting classifications of pathogenicity in CLRN1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.2432); Rare (popmax 0.771%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CLRN1 p.Ser3Arg (c.9C>A)?

CLRN1 p.Ser3Arg (c.9C>A) is associated with inherited retinal dystrophy, Usher syndrome type 3A (ClinVar).

How common is CLRN1 p.Ser3Arg (c.9C>A) in the general population?

CLRN1 p.Ser3Arg (c.9C>A) is rare (popmax 0.771%, eas) (gnomAD).

What do computational predictors say about CLRN1 p.Ser3Arg (c.9C>A)?

AlphaMissense predicts likely benign (score 0.2432) — an in-silico prediction, not a clinical call.

CLRN1 p.Ser3Arg

c.9C>A · rs187218889 · VCV48149

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.2432 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.771%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2432	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -7.51	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 4.1	GERP 0.76, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 45 kb · p 0.044 · regional, not allelic
Overall
CADD	17.16	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

Grpmax group 0.771% East Asian · 346/44,888 alleles

Filtering AF 0.704% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.678%

Overall 0.0254% 410/1,614,218 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.771%	130
Ashkenazi Jewishnot grpmax-eligible	0.0642%	1,558
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.0143%	7,007
Admixed American	0.00333%	30,012
European (non-Finnish)	0.000424%	236,008

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CLRN1
Protein: p.Ser3Arg
Coding: c.9C>A
MANE Select: NM_174878
dbSNP: rs187218889
Type: single nucleotide variant
Location: chr3:150972700 (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

Also linked: Usher syndrome type 3A

Similar variants

CLRN1 p.Ser3Asn Uncertain significance ★ ⚠ same residue
CLRN1 c.253+1G>A Likely pathogenic ★★ same condition
CLRN1 c.253+6T>C Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Ala123Asp Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Asn202Lys Pathogenic/Likely pathogenic ★★ same condition
CLRN1 p.Asn48Lys Pathogenic ★★ same condition
CLRN1 p.Gln181Ter 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-ser3arg (accessed [today's date]).

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