Is ARL6 p.Val103Phe (c.307G>T) pathogenic?

ARL6 p.Val103Phe (c.307G>T) is classified Uncertain significance in ARL6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-02). AlphaMissense: likely pathogenic (0.7468); Very rare (popmax 0.00407%, nfe); Associated with Bardet-Biedl syndrome 3.

What condition is associated with ARL6 p.Val103Phe (c.307G>T)?

ARL6 p.Val103Phe (c.307G>T) is associated with Bardet-Biedl syndrome 3, retinitis pigmentosa 55 (ClinVar).

How common is ARL6 p.Val103Phe (c.307G>T) in the general population?

ARL6 p.Val103Phe (c.307G>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

What do computational predictors say about ARL6 p.Val103Phe (c.307G>T)?

AlphaMissense predicts likely pathogenic (score 0.7468) — an in-silico prediction, not a clinical call.

ARL6 p.Val103Phe

c.307G>T · rs774150149 · VCV1483908

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome 3

Computational evidence

Protein change
AlphaMissense	0.7468	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -4.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 30 kb · p 0.057 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,179,378 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00298% 48/1,612,942 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.Val103Phe
Coding: c.307G>T
MANE Select: NM_001278293
dbSNP: rs774150149
Type: single nucleotide variant
Location: chr3:97785007 (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 103: an α-helix

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.Val103Ala 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-val103phe (accessed [today's date]).

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