Is RAB39B p.Arg177Ser (c.531G>T) pathogenic?

RAB39B p.Arg177Ser (c.531G>T) is classified Likely benign in RAB39B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: likely benign (0.2173); Ultra-rare (popmax 0.0197%, amr).

How common is RAB39B p.Arg177Ser (c.531G>T) in the general population?

RAB39B p.Arg177Ser (c.531G>T) is ultra-rare (popmax 0.0197%, amr) (gnomAD).

What do computational predictors say about RAB39B p.Arg177Ser (c.531G>T)?

AlphaMissense predicts likely benign (score 0.2173) — an in-silico prediction, not a clinical call.

RAB39B p.Arg177Ser

c.531G>T · VCV4873389

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2173 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2173	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP 0.018, phastCons 0.97
Regional constraint	o/e 0.40	unconstrained · MANE · 3,482 bp · p 2.9e-15 · regional, not allelic
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% Admixed American · 9/45,792 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00766%

Overall 0.00256% 31/1,209,555 alleles · ultra-rare exomes 27/1,097,710 · genomes 4/111,845 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0197%	5,088
African / African-American	0.00699%	14,308
East Asian	0.00296%	33,772
European (non-Finnish)	0.00179%	55,925
South Asian	0.00176%	56,766

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.Arg177Ser
Coding: c.531G>T
MANE Select: NM_171998
Type: single nucleotide variant
Location: chrX:155260914 (GRCh38)
Structure: AlphaFold pLDDT 88.67 · 1 PDB

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

Similar variants

RAB39B p.Arg177Lys Uncertain significance ★ ⚠ same residue
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

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-arg177ser (accessed [today's date]).

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