Is RAB33B p.Ala55= (c.165T>A) pathogenic?

RAB33B p.Ala55= (c.165T>A) is classified Uncertain significance in RAB33B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). Very rare (popmax 0.0022%, sas).

How common is RAB33B p.Ala55= (c.165T>A) in the general population?

RAB33B p.Ala55= (c.165T>A) is very rare (popmax 0.0022%, sas) (gnomAD).

RAB33B p.Ala55=

c.165T>A · VCV4968671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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
Pangolin	Δ0.30	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.12	GERP -3.8, phastCons 0.54
Overall
CADD	14.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,614,040 alleles · very rare exomes 2/1,461,788 · genomes 0/152,252 · 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: RAB33B
Protein: p.Ala55=
Coding: c.165T>A
MANE Select: NM_031296
Type: single nucleotide variant
Location: chr4:139454360 (GRCh38)
Gene constraint: LOEUF 0.774 · pLI 0.39 (gnomAD)
Structure: AlphaFold pLDDT 81.55 · 2 PDB
Residue 55: an α-helix

Full RAB33B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB33B p.Gln134Ter Pathogenic ★★ same type
RAB33B c.*2355T>A Uncertain significance ★★ same type
RAB33B p.Asn139Lys Uncertain significance ★★ ⚠ same type
RAB33B p.Asn185Asp Uncertain significance ★★ ⚠ same type
RAB33B p.Asn43Ser Uncertain significance ★★ ⚠ same type
RAB33B p.Ile191Met Uncertain significance ★★ ⚠ same type
RAB33B p.Ile33Leu Uncertain significance ★★ same type
RAB33B p.Leu49Val 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/rab33b-p-ala55 (accessed [today's date]).

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