Is RAB3GAP2 p.Arg420= (c.1260C>T) pathogenic?

RAB3GAP2 p.Arg420= (c.1260C>T) is classified Conflicting classifications of pathogenicity in RAB3GAP2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-16). Absent from gnomAD v4.1; Associated with Warburg micro syndrome 2.

What condition is associated with RAB3GAP2 p.Arg420= (c.1260C>T)?

RAB3GAP2 p.Arg420= (c.1260C>T) is associated with Warburg micro syndrome 2, Martsolf syndrome (ClinVar).

How common is RAB3GAP2 p.Arg420= (c.1260C>T) in the general population?

RAB3GAP2 p.Arg420= (c.1260C>T) is absent from gnomAD v4.1 (gnomAD).

RAB3GAP2 p.Arg420=

c.1260C>T · rs1658659314 · VCV963900

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Warburg micro syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.50	donor gain · deltas
Constraint at this position
Conservation	phyloP 4.5	GERP -0.99, phastCons 1
Overall
CADD	17.95	PHRED · no single calibrated threshold — expert panels disagree

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: RAB3GAP2
Protein: p.Arg420=
Coding: c.1260C>T
MANE Select: NM_012414
dbSNP: rs1658659314
Type: single nucleotide variant
Location: chr1:220193250 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB
Residue 420: a β-strand

Full RAB3GAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Warburg micro syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Martsolf syndrome

Similar variants

RAB3GAP2 p.Arg420Cys Uncertain significance ★★ ⚠ same residue
RAB3GAP2 p.Arg420His Uncertain significance ★ ⚠ same residue
RAB3GAP2 c.713-2A>C Likely pathogenic ★★ same condition
RAB3GAP2 p.Arg1213Ter Pathogenic ★★ same condition
RAB3GAP2 p.Arg426Cys Pathogenic/Likely pathogenic ★★ same condition
RAB3GAP2 c.*2171A>G Uncertain significance ★★ same condition
RAB3GAP2 p.Ala16Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala240Pro 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/rab3gap2-p-arg420 (accessed [today's date]).

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