Is CLRN1 p.Gln73Arg (c.218A>G) pathogenic?

CLRN1 p.Gln73Arg (c.218A>G) is classified Uncertain significance in CLRN1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0999); Ultra-rare (popmax 0.0347%, nfe); Associated with Usher syndrome type 3A.

What condition is associated with CLRN1 p.Gln73Arg (c.218A>G)?

CLRN1 p.Gln73Arg (c.218A>G) is associated with Usher syndrome type 3A, retinitis pigmentosa 61, inherited retinal dystrophy (ClinVar).

How common is CLRN1 p.Gln73Arg (c.218A>G) in the general population?

CLRN1 p.Gln73Arg (c.218A>G) is ultra-rare (popmax 0.0347%, nfe) (gnomAD).

What do computational predictors say about CLRN1 p.Gln73Arg (c.218A>G)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

CLRN1 p.Gln73Arg

c.218A>G · rs201008540 · VCV504559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Usher syndrome type 3A

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.583	indeterminate
SaProt	LLR -5.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 45 kb · p 0.044 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% European (non-Finnish) · 409/1,180,046 alleles

Filtering AF 0.0319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0307%

Overall 0.0273% 440/1,614,192 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0347%	2,885
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.0117%	8,575
African / African-American	0.00533%	18,760

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.Gln73Arg
Coding: c.218A>G
MANE Select: NM_174878
dbSNP: rs201008540
Type: single nucleotide variant
Location: chr3:150972491 (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: retinitis pigmentosa 61 inherited retinal dystrophy retinitis pigmentosa

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-gln73arg (accessed [today's date]).

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