Is RAB3GAP2 p.Lys1322= (c.3966A>G) pathogenic?

RAB3GAP2 p.Lys1322= (c.3966A>G) is classified Benign/Likely benign in RAB3GAP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-01). Rare (popmax 0.688%, afr); Associated with Warburg micro syndrome 2.

What condition is associated with RAB3GAP2 p.Lys1322= (c.3966A>G)?

RAB3GAP2 p.Lys1322= (c.3966A>G) is associated with Warburg micro syndrome 2, Martsolf syndrome (ClinVar).

How common is RAB3GAP2 p.Lys1322= (c.3966A>G) in the general population?

RAB3GAP2 p.Lys1322= (c.3966A>G) is rare (popmax 0.688%, afr) (gnomAD).

RAB3GAP2 p.Lys1322=

c.3966A>G · rs150226729 · VCV706153

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.688%, afr)

Conditions

Warburg micro syndrome 2

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
Constraint at this position
Conservation	phyloP -2	GERP -3.6
Overall
CADD	3.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.688% African / African-American · 516/74,978 alleles

Filtering AF 0.639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.62%

Overall 0.0366% 590/1,611,914 alleles · rare exomes 301/1,459,624 · genomes 289/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.688%	145
Admixed American	0.0583%	1,715
Remaining individualsnot grpmax-eligible	0.0384%	2,601
Middle Eastern	0.033%	3,031
South Asian	0.0011%	91,034
European (non-Finnish)	0.00102%	98,167

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: RAB3GAP2
Protein: p.Lys1322=
Coding: c.3966A>G
MANE Select: NM_012414
dbSNP: rs150226729
Type: single nucleotide variant
Location: chr1:220151666 (GRCh38)
Gene constraint: LOEUF 0.535 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.77 · 1 PDB

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 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
RAB3GAP2 p.Ala300Thr Uncertain significance ★★ ⚠ same condition
RAB3GAP2 p.Ala684Glu 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-lys1322 (accessed [today's date]).

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