Is RAB39A p.Arg76= (c.228A>G) pathogenic?

RAB39A p.Arg76= (c.228A>G) is classified Likely benign in RAB39A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.00343%, amr).

How common is RAB39A p.Arg76= (c.228A>G) in the general population?

RAB39A p.Arg76= (c.228A>G) is very rare (popmax 0.00343%, amr) (gnomAD).

RAB39A p.Arg76=

c.228A>G · VCV4575009

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00343%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP -1.8, phastCons 1
Overall
CADD	11.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00343% Admixed American · 2/58,330 alleles

Filtering AF 0.000569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000213%

Overall 0.000125% 2/1,599,934 alleles · very rare exomes 1/1,447,728 · genomes 1/152,206 · 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: RAB39A
Protein: p.Arg76=
Coding: c.228A>G
MANE Select: NM_017516
Type: single nucleotide variant
Location: chr11:107961946 (GRCh38)
Gene constraint: LOEUF 1.191 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58
Residue 76: the 'switch-ii' region

Full RAB39A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAB39A p.Arg139Ser Uncertain significance ★ same type
RAB39A p.Arg80Leu Uncertain significance ★ ⚠ same type
RAB39A p.Arg99Gln Uncertain significance ★ ⚠ same type
RAB39A p.Gln187His Uncertain significance ★ ⚠ same type
RAB39A p.Gly182Glu Uncertain significance ★ ⚠ same type
RAB39A p.Ile170Val Uncertain significance ★ ⚠ same type
RAB39A p.Met113Ile Uncertain significance ★ ⚠ same type
RAB39A p.Ser81Thr 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/rab39a-p-arg76 (accessed [today's date]).

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