Is RAB23 p.Lys31= (c.93A>G) pathogenic?

RAB23 p.Lys31= (c.93A>G) is classified Conflicting classifications of pathogenicity in RAB23 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-11). Rare (popmax 0.463%, eas); Associated with Carpenter syndrome.

What condition is associated with RAB23 p.Lys31= (c.93A>G)?

RAB23 p.Lys31= (c.93A>G) is associated with Carpenter syndrome, RAB23-related Carpenter syndrome (ClinVar).

How common is RAB23 p.Lys31= (c.93A>G) in the general population?

RAB23 p.Lys31= (c.93A>G) is rare (popmax 0.463%, eas) (gnomAD).

RAB23 p.Lys31=

c.93A>G · rs201735614 · VCV908659

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.463%, eas)

Conditions

Carpenter syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.57, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.463% East Asian · 208/44,880 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.392%

Overall 0.0136% 219/1,614,086 alleles · rare exomes 209/1,461,738 · genomes 10/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.463%	216
Middle Eastern	0.033%	3,031
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0016%	62,504
Finnishnot grpmax-eligible	0.00156%	64,018
European (non-Finnish)	0.00017%	589,971

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.Lys31=
Coding: c.93A>G
MANE Select: NM_016277
dbSNP: rs201735614
Type: single nucleotide variant
Location: chr6:57210288 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.39 · 6 PDB
Residue 31: an α-helix

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

Also linked: RAB23-related Carpenter syndrome

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.Ser206Thr 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-lys31 (accessed [today's date]).

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