Is RAB3GAP2 p.Phe1216= (c.3648C>T) pathogenic?

RAB3GAP2 p.Phe1216= (c.3648C>T) is classified Likely benign in RAB3GAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0111%, eas); Associated with Martsolf syndrome.

What condition is associated with RAB3GAP2 p.Phe1216= (c.3648C>T)?

RAB3GAP2 p.Phe1216= (c.3648C>T) is associated with Martsolf syndrome, Warburg micro syndrome 2 (ClinVar).

How common is RAB3GAP2 p.Phe1216= (c.3648C>T) in the general population?

RAB3GAP2 p.Phe1216= (c.3648C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

RAB3GAP2 p.Phe1216=

c.3648C>T · rs745868602 · VCV753091

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Conditions

Martsolf syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 1, phastCons 1
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,880 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00124% 20/1,613,176 alleles · ultra-rare exomes 16/1,461,050 · genomes 4/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,976
Admixed American	0.00333%	29,992
African / African-American	0.00134%	74,890
European (non-Finnish)	0.00102%	98,274

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.Phe1216=
Coding: c.3648C>T
MANE Select: NM_012414
dbSNP: rs745868602
Type: single nucleotide variant
Location: chr1:220153404 (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

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

Also linked: Warburg micro syndrome 2

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-phe1216 (accessed [today's date]).

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