Is CLRN1 p.Arg82Gln (c.245G>A) pathogenic?

CLRN1 p.Arg82Gln (c.245G>A) is classified Uncertain significance in CLRN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-12). AlphaMissense: likely benign (0.0656); Ultra-rare (popmax 0.033%, mid).

How common is CLRN1 p.Arg82Gln (c.245G>A) in the general population?

CLRN1 p.Arg82Gln (c.245G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CLRN1 p.Arg82Gln (c.245G>A)?

AlphaMissense predicts likely benign (score 0.0656) — an in-silico prediction, not a clinical call.

CLRN1 p.Arg82Gln

c.245G>A · rs765946379 · VCV2155690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0656 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0656	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.05	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 -0.08	GERP 0.82
Regional constraint	o/e 1.12	unconstrained · MANE · 45 kb · p 0.044 · regional, not allelic
Overall
CADD	18.2	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000752% 11/1,461,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.000593%	168,575

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.Arg82Gln
Coding: c.245G>A
MANE Select: NM_174878
dbSNP: rs765946379
Type: single nucleotide variant
Location: chr3:150972464 (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

Similar variants

CLRN1 p.Arg82Gly Uncertain significance ★★ ⚠ same residue
CLRN1 p.Arg82= Likely benign ★ same residue
CLRN1 c.253+1G>A Likely pathogenic ★★ same type
CLRN1 c.253+6T>C Pathogenic/Likely pathogenic ★★ same type
CLRN1 c.254-2A>G Pathogenic/Likely pathogenic ★★ same type
CLRN1 c.254-649T>G Pathogenic/Likely pathogenic ★★ same type
CLRN1 c.433+1G>A Pathogenic/Likely pathogenic ★★ same type
CLRN1 c.433+1G>T Likely pathogenic ★★ same type

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-arg82gln (accessed [today's date]).

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