Is CLRN3 p.His90Arg (c.269A>G) pathogenic?

CLRN3 p.His90Arg (c.269A>G) is classified Uncertain significance in CLRN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: ambiguous (0.507); Absent from gnomAD v4.1.

How common is CLRN3 p.His90Arg (c.269A>G) in the general population?

CLRN3 p.His90Arg (c.269A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLRN3 p.His90Arg (c.269A>G)?

AlphaMissense predicts ambiguous (score 0.507) — an in-silico prediction, not a clinical call.

CLRN3 p.His90Arg

c.269A>G · rs756403169 · VCV2281591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.507 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.507	ambiguous
REVEL	0.347	indeterminate
SaProt	LLR -10.05	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 15 kb · p 0.19 · regional, not allelic
Overall
CADD	14.12	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: CLRN3
Protein: p.His90Arg
Coding: c.269A>G
MANE Select: NM_152311
dbSNP: rs756403169
Type: single nucleotide variant
Location: chr10:127883836 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.68

Full CLRN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLRN3 p.Ala149Glu Uncertain significance ★ ⚠ same type
CLRN3 p.Ala149Ser Uncertain significance ★ ⚠ same type
CLRN3 p.Ala149Thr Uncertain significance ★ ⚠ same type
CLRN3 p.Ala149Val Uncertain significance ★ ⚠ same type
CLRN3 p.Arg208Trp Uncertain significance ★ ⚠ same type
CLRN3 p.Asn46His Uncertain significance ★ ⚠ same type
CLRN3 p.Gln207Arg Uncertain significance ★ ⚠ same type
CLRN3 p.Gln31Pro Uncertain significance ★ ⚠ 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/clrn3-p-his90arg (accessed [today's date]).

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