Is RNF2 p.Ser82Arg (c.246T>G) pathogenic?

RNF2 p.Ser82Arg (c.246T>G) is classified Pathogenic in RNF2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-19). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1; Associated with Luo-Schoch-Yamamoto syndrome.

What condition is associated with RNF2 p.Ser82Arg (c.246T>G)?

RNF2 p.Ser82Arg (c.246T>G) is associated with Luo-Schoch-Yamamoto syndrome (ClinVar).

How common is RNF2 p.Ser82Arg (c.246T>G) in the general population?

RNF2 p.Ser82Arg (c.246T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RNF2 p.Ser82Arg (c.246T>G)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

RNF2 p.Ser82Arg

c.246T>G · rs1651768254 · VCV1189036

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Luo-Schoch-Yamamoto syndrome

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic ✓ concordant with ClinVar
REVEL	0.595	indeterminate
SaProt	LLR -11.83	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.62	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.47	GERP -2, phastCons 1
Regional constraint	o/e 0.10	constrained · MANE · 1,419 bp · p 1.3e-08 · regional, not allelic
Overall
CADD	24.8	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.Ser82Arg
Coding: c.246T>G
MANE Select: NM_007212
dbSNP: rs1651768254
Type: single nucleotide variant
Location: chr1:185091737 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 28 PDB
Residue 82: a UniProt-annotated variant site (in lusyam; uncertain significance); the 'interaction with hip2' region; a turn

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.Phe82Cys Uncertain significance ★ ⚠ same residue
RNF2 c.465-1G>A Uncertain significance ★ same condition
RNF2 p.Arg70His Uncertain significance ★ ⚠ same condition
RNF2 p.Thr197Ile Uncertain significance ★ ⚠ same condition
RNF2 p.Tyr247His Uncertain significance ★ ⚠ same condition
RNF2 p.Val127Ile Uncertain significance ★ ⚠ same condition
RNF2 p.Val256Leu Uncertain significance ★ ⚠ same condition
RNF2 p.Gln301Arg 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-ser82arg (accessed [today's date]).

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