Is ARL6 p.Gln43= (c.129A>G) pathogenic?

ARL6 p.Gln43= (c.129A>G) is classified Likely benign in ARL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). Very rare (popmax 8.48e-05%, nfe); Associated with Bardet-Biedl syndrome 3.

What condition is associated with ARL6 p.Gln43= (c.129A>G)?

ARL6 p.Gln43= (c.129A>G) is associated with Bardet-Biedl syndrome 3, retinitis pigmentosa 55 (ClinVar).

How common is ARL6 p.Gln43= (c.129A>G) in the general population?

ARL6 p.Gln43= (c.129A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

ARL6 p.Gln43=

c.129A>G · rs1233384287 · VCV2942483

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Bardet-Biedl syndrome 3

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 0.67	GERP -1.6, phastCons 0.95
Overall
CADD	7.285	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,722 alleles

Overall 6.85e-05% 1/1,460,176 alleles · very rare

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: ARL6
Protein: p.Gln43=
Coding: c.129A>G
MANE Select: NM_001278293
dbSNP: rs1233384287
Type: single nucleotide variant
Location: chr3:97780164 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.81 · 1 PDB

Full ARL6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 55

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

ARL6 p.Gln43Ter Pathogenic ★ same residue
ARL6 c.185+1G>C Pathogenic ★★ same condition
ARL6 c.255-2A>T Pathogenic ★★ same condition
ARL6 c.349+1G>A Likely pathogenic ★★ same condition
ARL6 c.350-2A>C Pathogenic/Likely pathogenic ★★ same condition
ARL6 p.Arg121His Pathogenic/Likely pathogenic ★★ ⚠ same condition
ARL6 p.Arg122Ter Pathogenic ★★ same condition
ARL6 p.Gln178= Pathogenic/Likely pathogenic ★★ 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/arl6-p-gln43 (accessed [today's date]).

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