Is RNF2 p.Gln301Arg (c.902A>G) pathogenic?

RNF2 p.Gln301Arg (c.902A>G) is classified Uncertain significance in RNF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-20). AlphaMissense: ambiguous (0.427); Absent from gnomAD v4.1; Associated with Luo-Schoch-Yamamoto syndrome.

What condition is associated with RNF2 p.Gln301Arg (c.902A>G)?

RNF2 p.Gln301Arg (c.902A>G) is associated with Luo-Schoch-Yamamoto syndrome (ClinVar).

How common is RNF2 p.Gln301Arg (c.902A>G) in the general population?

RNF2 p.Gln301Arg (c.902A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF2 p.Gln301Arg (c.902A>G)?

AlphaMissense predicts ambiguous (score 0.427) — an in-silico prediction, not a clinical call.

RNF2 p.Gln301Arg

c.902A>G · rs2526103636 · VCV3066073

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.427 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Luo-Schoch-Yamamoto syndrome

Computational evidence

Protein change
AlphaMissense	0.427	ambiguous
REVEL	0.719	pathogenic-leaning
SaProt	LLR -8.54	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 413 bp · p 0.22 · regional, not allelic
Overall
CADD	25.0	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: RNF2
Protein: p.Gln301Arg
Coding: c.902A>G
MANE Select: NM_007212
dbSNP: rs2526103636
Type: single nucleotide variant
Location: chr1:185099955 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 28 PDB

Full RNF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Luo-Schoch-Yamamoto syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAP1 p.Ala301= Likely benign ★★ same residue
BAP1 p.Ala301Asp Uncertain significance ★ ⚠ same residue
BAP1 p.Ala301Gly Uncertain significance ★ ⚠ same residue
BAP1 p.Ala301Thr Uncertain significance ★ ⚠ same residue
BAP1 p.Ala301Val Uncertain significance ★ ⚠ same residue
BAP1 p.Ala301Ser Benign ★ same residue
RNF2 c.465-1G>A Uncertain significance ★ same condition
RNF2 p.Arg70His Uncertain significance ★ ⚠ 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/rnf2-p-gln301arg (accessed [today's date]).

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