Is CLRN1 p.Ala19= (c.57A>T) pathogenic?

CLRN1 p.Ala19= (c.57A>T) is classified Benign/Likely benign in CLRN1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 21.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 3A.

What condition is associated with CLRN1 p.Ala19= (c.57A>T)?

CLRN1 p.Ala19= (c.57A>T) is associated with Usher syndrome type 3A, Usher syndrome type 3, inherited retinal dystrophy (ClinVar).

CLRN1 p.Ala19=

Q: How common is CLRN1 p.Ala19= (c.57A>T) in the general population?

CLRN1 p.Ala19= (c.57A>T) is common (popmax 21.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.57A>T · rs3796242 · VCV48147

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 21.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Usher syndrome type 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -2.6
Overall
CADD	9.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.6% East Asian · 9,696/44,884 alleles

Filtering AF 21.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.1%

Overall 12.3% 198,588/1,614,088 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	21.6%	5
Finnishnot grpmax-eligible	18.7%	5
Admixed American	15.8%	6
Amishnot grpmax-eligible	14%	7
Remaining individualsnot grpmax-eligible	12.7%	8
European (non-Finnish)	11.9%	8
Middle Eastern	11%	9
South Asian	9.89%	10
African / African-American	8.85%	11
Ashkenazi Jewishnot grpmax-eligible	7.62%	13

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.Ala19=
Coding: c.57A>T
MANE Select: NM_174878
dbSNP: rs3796242
Type: single nucleotide variant
Location: chr3:150972652 (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 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 3 inherited retinal dystrophy

Similar variants

CLRN1 c.253+1G>A Likely pathogenic ★★ same condition
CLRN1 c.253+6T>C Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.254-2A>G Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.433+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLRN1 c.433+1G>T 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

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-ala19 (accessed [today's date]).

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