Is RAB23 p.Pro219Ser (c.655C>T) pathogenic?

RAB23 p.Pro219Ser (c.655C>T) is classified Uncertain significance in RAB23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.5842); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RAB23 p.Pro219Ser (c.655C>T)?

RAB23 p.Pro219Ser (c.655C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RAB23 p.Pro219Ser (c.655C>T) in the general population?

RAB23 p.Pro219Ser (c.655C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about RAB23 p.Pro219Ser (c.655C>T)?

AlphaMissense predicts likely pathogenic (score 0.5842) — an in-silico prediction, not a clinical call.

RAB23 p.Pro219Ser

c.655C>T · VCV4149253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5842	likely pathogenic
REVEL	0.389	indeterminate
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 20 kb · p 0.051 · regional, not allelic
Overall
CADD	24.4	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 0.00102% European (non-Finnish) · 12/1,179,900 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,834 alleles · very rare exomes 10/1,461,716 · genomes 2/152,118 · 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.Pro219Ser
Coding: c.655C>T
MANE Select: NM_016277
Type: single nucleotide variant
Location: chr6:57190520 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.39 · 6 PDB
Residue 219: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAB23 p.Gln204Arg Uncertain significance ★★ ⚠ same condition
RAB23 p.Ala138Thr Uncertain significance ★ ⚠ same condition
RAB23 p.Ala178Ser Uncertain significance ★ ⚠ same condition
RAB23 p.Arg142Thr Uncertain significance ★ ⚠ same condition
RAB23 p.Asn216Ser Uncertain significance ★ ⚠ same condition
RAB23 p.Glu179Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
RAB23 p.Glu182Gln Uncertain significance ★ ⚠ same condition
RAB23 p.Ile114Leu 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-pro219ser (accessed [today's date]).

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