Is RAB39B p.Ser47fs (c.137dup) pathogenic?

RAB39B p.Ser47fs (c.137dup) is classified Pathogenic in RAB39B (ClinVar, Single submitter, 2 submitters; last evaluated 2026-07-31). Very rare (popmax 0.000112%, nfe); Associated with intellectual disability, X-linked 72.

What condition is associated with RAB39B p.Ser47fs (c.137dup)?

RAB39B p.Ser47fs (c.137dup) is associated with intellectual disability, X-linked 72 (ClinVar).

How common is RAB39B p.Ser47fs (c.137dup) in the general population?

RAB39B p.Ser47fs (c.137dup) is very rare (popmax 0.000112%, nfe) (gnomAD).

RAB39B p.Ser47fs

c.137dup · rs2124130091 · VCV1691598

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

intellectual disability, X-linked 72

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,482 alleles

Overall 8.25e-05% 1/1,212,079 alleles · very rare exomes 1/1,098,124 · genomes 0/113,955 · 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: RAB39B
Protein: p.Ser47fs
Coding: c.137dup
MANE Select: NM_171998
dbSNP: rs2124130091
Type: Duplication
Location: chrX:155264151 (GRCh38)
Structure: AlphaFold pLDDT 88.67 · 1 PDB
Residue 47: a β-strand

Full RAB39B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 72 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB39B p.Ser47Thr Uncertain significance ★ ⚠ same residue
RAB39B p.Ser96Phe Uncertain significance ★★ ⚠ same condition
RAB39B p.Thr129Ile Uncertain significance ★★ ⚠ same condition
RAB39B c.*1347C>T Benign ★★ same condition
RAB39B c.*1656= Benign ★★ same condition
RAB39B p.Thr181= Benign/Likely benign ★★ same condition
RAB39B p.Ala144del Likely pathogenic ★ same condition
RAB39B p.Glu187Ter Pathogenic ★ 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/rab39b-p-ser47fs (accessed [today's date]).

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