Is RAB34 p.Pro5Ser (c.13C>T) pathogenic?

RAB34 p.Pro5Ser (c.13C>T) is classified Uncertain significance in RAB34 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). Very rare (popmax 0.00137%, afr).

How common is RAB34 p.Pro5Ser (c.13C>T) in the general population?

RAB34 p.Pro5Ser (c.13C>T) is very rare (popmax 0.00137%, afr) (gnomAD).

RAB34 p.Pro5Ser

c.13C>T · VCV4574991

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.213	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.8, phastCons 0.74
Overall
CADD	15.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% African / African-American · 1/73,226 alleles

Overall 0.000128% 2/1,559,244 alleles · very rare exomes 2/1,406,928 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00137%	73,226
South Asian	0.00118%	85,076

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.Pro5Ser
Coding: c.13C>T
MANE Select: NM_031934 · reported on NM_001144943
Type: single nucleotide variant
Location: chr17:28718255 (GRCh38)
Gene constraint: LOEUF 1.152 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.94

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-pro5ser (accessed [today's date]).

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