Is RAB23 p.Ser197Phe (c.590C>T) pathogenic?

RAB23 p.Ser197Phe (c.590C>T) is classified Uncertain significance in RAB23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-08). AlphaMissense: likely benign (0.1571); Very rare (popmax 0.000254%, nfe); Associated with Carpenter syndrome.

What condition is associated with RAB23 p.Ser197Phe (c.590C>T)?

RAB23 p.Ser197Phe (c.590C>T) is associated with Carpenter syndrome (ClinVar).

How common is RAB23 p.Ser197Phe (c.590C>T) in the general population?

RAB23 p.Ser197Phe (c.590C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about RAB23 p.Ser197Phe (c.590C>T)?

AlphaMissense predicts likely benign (score 0.1571) — an in-silico prediction, not a clinical call.

RAB23 p.Ser197Phe

c.590C>T · rs2127996379 · VCV1354497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1571 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Carpenter syndrome

Computational evidence

Protein change
AlphaMissense	0.1571	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -8.60	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 10	GERP 2.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 20 kb · p 0.051 · regional, not allelic
Overall
CADD	23.5	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 0.000254% European (non-Finnish) · 3/1,179,924 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,026 alleles · very rare exomes 3/1,461,740 · genomes 0/152,286 · 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.Ser197Phe
Coding: c.590C>T
MANE Select: NM_016277
dbSNP: rs2127996379
Type: single nucleotide variant
Location: chr6:57190585 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.39 · 6 PDB
Residue 197: 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

Carpenter syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB23 p.Arg28Ter Pathogenic/Likely pathogenic ★★ same condition
RAB23 p.Arg49Ter Pathogenic/Likely pathogenic ★★ same condition
RAB23 p.Arg80Ter Pathogenic/Likely pathogenic ★★ same condition
RAB23 p.Leu145Ter Pathogenic ★★ same condition
RAB23 c.481+4A>C Uncertain significance ★★ same condition
RAB23 p.Cys30Trp Uncertain significance ★★ ⚠ same condition
RAB23 p.Gly203Ser Uncertain significance ★★ ⚠ same condition
RAB23 p.Thr116Ala 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-ser197phe (accessed [today's date]).

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