Is RAB23 p.Val193Phe (c.577G>T) pathogenic?

RAB23 p.Val193Phe (c.577G>T) is classified Uncertain significance in RAB23 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely benign (0.2019); Very rare (popmax 0.00333%, amr); Associated with RAB23-related disorder.

What condition is associated with RAB23 p.Val193Phe (c.577G>T)?

RAB23 p.Val193Phe (c.577G>T) is associated with RAB23-related disorder (ClinVar).

How common is RAB23 p.Val193Phe (c.577G>T) in the general population?

RAB23 p.Val193Phe (c.577G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about RAB23 p.Val193Phe (c.577G>T)?

AlphaMissense predicts likely benign (score 0.2019) — an in-silico prediction, not a clinical call.

RAB23 p.Val193Phe

c.577G>T · VCV3348277

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

RAB23-related disorder

Computational evidence

Protein change
AlphaMissense	0.2019	likely benign
REVEL	0.316	indeterminate
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 20 kb · p 0.051 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00333% Admixed American · 2/60,018 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,954 alleles · very rare exomes 2/1,461,664 · genomes 0/152,290 · 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: RAB23
Protein: p.Val193Phe
Coding: c.577G>T
MANE Select: NM_016277
Type: single nucleotide variant
Location: chr6:57190598 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.39 · 6 PDB
Residue 193: the 'disordered' region; a UniProt-annotated variant site (in crpt1; pathogenic; homozygous patient-derived neuronal cells exhibit impaired formation of the primary cilium)

Full RAB23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RAB23-related disorder

Similar variants

RAB23 p.Leu145Ter Pathogenic ★★ same condition
RAB23 p.Cys30Trp Uncertain significance ★★ ⚠ same condition
RAB23 c.575-10A>G Uncertain significance same condition
RAB23 p.Arg218Thr Uncertain significance ⚠ same condition
RAB23 p.Asp5Glu Uncertain significance ⚠ same condition
RAB23 p.Gln222Lys Uncertain significance ⚠ same condition
RAB23 p.Gly112Val Uncertain significance ⚠ same condition
RAB23 p.Gly203Asp 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/rab23-p-val193phe (accessed [today's date]).

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