Is ARL13B p.Tyr320Phe (c.959A>T) pathogenic?

ARL13B p.Tyr320Phe (c.959A>T) is classified Uncertain significance in ARL13B (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-14). AlphaMissense: likely benign (0.1272); Absent from gnomAD v4.1; Associated with Joubert syndrome 8.

What condition is associated with ARL13B p.Tyr320Phe (c.959A>T)?

ARL13B p.Tyr320Phe (c.959A>T) is associated with Joubert syndrome 8 (ClinVar).

How common is ARL13B p.Tyr320Phe (c.959A>T) in the general population?

ARL13B p.Tyr320Phe (c.959A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARL13B p.Tyr320Phe (c.959A>T)?

AlphaMissense predicts likely benign (score 0.1272) — an in-silico prediction, not a clinical call.

ARL13B p.Tyr320Phe

c.959A>T · rs2076893582 · VCV967493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1272 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome 8

Computational evidence

Protein change
AlphaMissense	0.1272	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.4, phastCons 0.3
Regional constraint	o/e 1.02	unconstrained · MANE · 73 kb · p 0.6 · regional, not allelic
Overall
CADD	14.62	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

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: ARL13B
Protein: p.Tyr320Phe
Coding: c.959A>T
MANE Select: NM_001174150
dbSNP: rs2076893582
Type: single nucleotide variant
Location: chr3:94043175 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.92
Residue 320: the 'disordered' region

Full ARL13B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARL13B c.1141+1G>A Likely pathogenic ★★ same condition
ARL13B c.131-1G>T Pathogenic/Likely pathogenic ★★ same condition
ARL13B p.Arg200Cys Pathogenic/Likely pathogenic ★★ same condition
ARL13B p.Cys287Ter Pathogenic/Likely pathogenic ★★ same condition
ARL13B p.Gln258Ter Pathogenic/Likely pathogenic ★★ same condition
ARL13B p.Gly75Arg Pathogenic ★★ same condition
ARL13B c.1211-1G>C Uncertain significance ★★ same condition
ARL13B p.Ala210Val Uncertain significance ★★ ⚠ 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/arl13b-p-tyr320phe (accessed [today's date]).

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