Is RNF2 p.Lys336= (c.1008A>G) pathogenic?

RNF2 p.Lys336= (c.1008A>G) is classified Uncertain significance in RNF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). Very rare (popmax 0.000425%, nfe); Associated with RNF2-related disorder.

What condition is associated with RNF2 p.Lys336= (c.1008A>G)?

RNF2 p.Lys336= (c.1008A>G) is associated with RNF2-related disorder (ClinVar).

How common is RNF2 p.Lys336= (c.1008A>G) in the general population?

RNF2 p.Lys336= (c.1008A>G) is very rare (popmax 0.000425%, nfe) (gnomAD).

RNF2 p.Lys336=

c.1008A>G · rs1652041854 · VCV2633881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

RNF2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.89	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.1	GERP -0.55, phastCons 1
Overall
CADD	10.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,175,688 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000312% 5/1,602,022 alleles · very rare exomes 5/1,449,718 · genomes 0/152,304 · joint denominator

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: RNF2
Protein: p.Lys336=
Coding: c.1008A>G
MANE Select: NM_007212
dbSNP: rs1652041854
Type: single nucleotide variant
Location: chr1:185100298 (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

RNF2-related disorder

Similar variants

BAP1 p.Val336Ala Uncertain significance ★★ ⚠ same residue
BAP1 p.Val336Gly Uncertain significance ★ ⚠ same residue
BAP1 p.Val336Leu Uncertain significance ★ ⚠ same residue
BAP1 p.Met1Arg Pathogenic/Likely pathogenic ★★ same condition
BAP1 p.Ile263Val Uncertain significance ★★ ⚠ same condition
BAP1 p.Ser455Pro Uncertain significance ★★ ⚠ same condition
BAP1 p.Tyr33His Likely pathogenic ★ same condition
BAP1 p.Arg545His Conflicting classifications of pathogenicity ★ 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-lys336 (accessed [today's date]).

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