Is RAB39B p.Phe89Cys (c.266T>G) pathogenic?

RAB39B p.Phe89Cys (c.266T>G) is classified Uncertain significance in RAB39B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-11). AlphaMissense: likely pathogenic (0.9908); Absent from gnomAD v4.1.

How common is RAB39B p.Phe89Cys (c.266T>G) in the general population?

RAB39B p.Phe89Cys (c.266T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAB39B p.Phe89Cys (c.266T>G)?

AlphaMissense predicts likely pathogenic (score 0.9908) — an in-silico prediction, not a clinical call.

RAB39B p.Phe89Cys

c.266T>G · VCV3367858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9908 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9908	likely pathogenic
REVEL	0.94	strongly pathogenic-leaning
SaProt	LLR -13.39	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 3,482 bp · p 2.9e-15 · regional, not allelic
Overall
CADD	26.7	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.Phe89Cys
Coding: c.266T>G
MANE Select: NM_171998
Type: single nucleotide variant
Location: chrX:155261179 (GRCh38)
Structure: AlphaFold pLDDT 88.67 · 1 PDB
Residue 89: a β-strand

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

Similar variants

RAB39B p.Gly178Arg Uncertain significance ★★ ⚠ same type
RAB39B p.Ser96Phe Uncertain significance ★★ ⚠ same type
RAB39B p.Thr129Ile Uncertain significance ★★ ⚠ same type
RAB39B c.*1347C>T Benign ★★ same type
RAB39B c.*1656= Benign ★★ same type
RAB39B p.Gly31= Benign/Likely benign ★★ same type
RAB39B p.Gly42= Benign/Likely benign ★★ same type
RAB39B p.His110= Benign/Likely benign ★★ same type

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-phe89cys (accessed [today's date]).

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