Is ARL6 p.His158= (c.474T>C) pathogenic?

ARL6 p.His158= (c.474T>C) is classified Likely benign in ARL6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-08). Ultra-rare (popmax 0.0307%, afr); Associated with Bardet-Biedl syndrome 3.

What condition is associated with ARL6 p.His158= (c.474T>C)?

ARL6 p.His158= (c.474T>C) is associated with Bardet-Biedl syndrome 3, retinitis pigmentosa 55 (ClinVar).

How common is ARL6 p.His158= (c.474T>C) in the general population?

ARL6 p.His158= (c.474T>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

ARL6 p.His158=

c.474T>C · rs141305892 · VCV2928646

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Conditions

Bardet-Biedl syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.369	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -3.6, phastCons 1
Overall
CADD	5.917	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,882 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00161% 26/1,612,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,256
Admixed American	0.00334%	29,966
European (non-Finnish)	8.48e-05%	1,179,478

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.His158=
Coding: c.474T>C
MANE Select: NM_001278293
dbSNP: rs141305892
Type: single nucleotide variant
Location: chr3:97788114 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 94.81 · 1 PDB
Residue 158: a β-strand

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.His158Arg Uncertain significance ⚠ 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-his158 (accessed [today's date]).

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