Is CLRN3 p.Gln31Pro (c.92A>C) pathogenic?

CLRN3 p.Gln31Pro (c.92A>C) is classified Uncertain significance in CLRN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely benign (0.0705); Absent from gnomAD v4.1.

How common is CLRN3 p.Gln31Pro (c.92A>C) in the general population?

CLRN3 p.Gln31Pro (c.92A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLRN3 p.Gln31Pro (c.92A>C)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

CLRN3 p.Gln31Pro

c.92A>C · rs2493647557 · VCV2533852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.13	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 0.27	GERP -0.95, phastCons 0.019
Regional constraint	o/e 1.08	unconstrained · MANE · 15 kb · p 0.19 · regional, not allelic
Overall
CADD	6.38	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

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.Gln31Pro
Coding: c.92A>C
MANE Select: NM_152311
dbSNP: rs2493647557
Type: single nucleotide variant
Location: chr10:127892693 (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.Glu158Lys 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-gln31pro (accessed [today's date]).

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