Is ARL6 p.Met1Val (c.1A>G) pathogenic?

ARL6 p.Met1Val (c.1A>G) is classified Pathogenic in ARL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). Absent from gnomAD v4.1; Associated with Bardet-Biedl syndrome 3.

What condition is associated with ARL6 p.Met1Val (c.1A>G)?

ARL6 p.Met1Val (c.1A>G) is associated with Bardet-Biedl syndrome 3, retinitis pigmentosa 55 (ClinVar).

How common is ARL6 p.Met1Val (c.1A>G) in the general population?

ARL6 p.Met1Val (c.1A>G) is absent from gnomAD v4.1 (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

ARL6 p.Met1Val

c.1A>G · rs2107977736 · VCV1446585

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bardet-Biedl syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.596	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 0.96, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARL6
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_001278293
dbSNP: rs2107977736
Type: single nucleotide variant
Location: chr3:97768108 (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 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
ARL6 p.Gly169Ala 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-met1val (accessed [today's date]).

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