Is ARL6 p.Ser8= (c.24A>C) pathogenic?

ARL6 p.Ser8= (c.24A>C) is classified Likely benign in ARL6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). Very rare (popmax 0.00223%, eas); Associated with retinitis pigmentosa 55.

What condition is associated with ARL6 p.Ser8= (c.24A>C)?

ARL6 p.Ser8= (c.24A>C) is associated with retinitis pigmentosa 55, Bardet-Biedl syndrome 3 (ClinVar).

How common is ARL6 p.Ser8= (c.24A>C) in the general population?

ARL6 p.Ser8= (c.24A>C) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

ARL6 p.Ser8=

c.24A>C · rs776814564 · VCV2948643

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

retinitis pigmentosa 55

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 0.93	GERP -3.6, phastCons 0.98
Overall
CADD	6.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,818 alleles

Overall 6.85e-05% 1/1,460,874 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.Ser8=
Coding: c.24A>C
MANE Select: NM_001278293
dbSNP: rs776814564
Type: single nucleotide variant
Location: chr3:97768131 (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

retinitis pigmentosa 55 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 3

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

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-ser8 (accessed [today's date]).

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