Is RAB39B p.Ser22Ala (c.64T>G) pathogenic?

RAB39B p.Ser22Ala (c.64T>G) is classified Uncertain significance in RAB39B (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-06). AlphaMissense: likely pathogenic (0.9647); Absent from gnomAD v4.1; Associated with intellectual disability, X-linked 72.

What condition is associated with RAB39B p.Ser22Ala (c.64T>G)?

RAB39B p.Ser22Ala (c.64T>G) is associated with intellectual disability, X-linked 72 (ClinVar).

How common is RAB39B p.Ser22Ala (c.64T>G) in the general population?

RAB39B p.Ser22Ala (c.64T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAB39B p.Ser22Ala (c.64T>G)?

AlphaMissense predicts likely pathogenic (score 0.9647) — an in-silico prediction, not a clinical call.

RAB39B p.Ser22Ala

c.64T>G · rs2074862064 · VCV931638

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9647 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 72

Computational evidence

Protein change
AlphaMissense	0.9647	likely pathogenic
REVEL	0.76	pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP -0.98, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 3,482 bp · p 2.9e-15 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: RAB39B
Protein: p.Ser22Ala
Coding: c.64T>G
MANE Select: NM_171998
dbSNP: rs2074862064
Type: single nucleotide variant
Location: chrX:155264225 (GRCh38)
Structure: AlphaFold pLDDT 88.67 · 1 PDB
Residue 22: an α-helix; a binding site

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.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.Glu187Ter Pathogenic ★ same condition
RAB39B c.-62C>A Uncertain significance ★ same condition
RAB39B c.*1428T>G 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/rab39b-p-ser22ala (accessed [today's date]).

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