Is RAB34 p.Gln18Pro (c.53A>C) pathogenic?

RAB34 p.Gln18Pro (c.53A>C) is classified Uncertain significance in RAB34 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0606); Very rare (popmax 8.49e-05%, nfe).

How common is RAB34 p.Gln18Pro (c.53A>C) in the general population?

RAB34 p.Gln18Pro (c.53A>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about RAB34 p.Gln18Pro (c.53A>C)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

RAB34 p.Gln18Pro

c.53A>C · rs1023223196 · VCV3150679

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -4.03	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 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,620 bp · p 0.04 · regional, not allelic
Overall
CADD	24.2	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 8.49e-05% European (non-Finnish) · 1/1,177,736 alleles

Overall 6.24e-05% 1/1,603,284 alleles · very rare exomes 1/1,451,002 · genomes 0/152,282 · 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: RAB34
Protein: p.Gln18Pro
Coding: c.53A>C
MANE Select: NM_031934
dbSNP: rs1023223196
Type: single nucleotide variant
Location: chr17:28717214 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.94
Residue 18: the '13 x 9 aa approximate tandem-repeats of p-r-v-i-v-g-(s/t)-p-r' region

Full RAB34 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB34 p.Arg231Ter Likely pathogenic ★ same type
RAB34 p.Ile85Thr Likely pathogenic ★ same type
RAB34 p.Ala213Gly Uncertain significance ★ ⚠ same type
RAB34 p.Ala213Ser Uncertain significance ★ ⚠ same type
RAB34 p.Arg123Lys Uncertain significance ★ ⚠ same type
RAB34 p.Arg211Cys Uncertain significance ★ ⚠ same type
RAB34 p.Arg232Cys Uncertain significance ★ ⚠ same type
RAB34 p.Arg33Gly Uncertain significance ★ 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/rab34-p-gln18pro (accessed [today's date]).

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