Is ARL13B p.Phe2fs (c.4_7delinsGCCAGTTG) pathogenic?

ARL13B p.Phe2fs (c.47delinsGCCAGTTG) is classified Likely pathogenic in ARL13B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-25). Associated with ARL13B-related disorder.

What condition is associated with ARL13B p.Phe2fs (c.4_7delinsGCCAGTTG)?

ARL13B p.Phe2fs (c.4_7delinsGCCAGTTG) is associated with ARL13B-related disorder (ClinVar).

ARL13B p.Phe2fs

c.4_7delinsGCCAGTTG · VCV4963404

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ARL13B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.78	GERP 0.76, phastCons 1

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

Variant & gene context

Gene: ARL13B
Protein: p.Phe2fs
Coding: c.4_7delinsGCCAGTTG
MANE Select: NM_001174150
Type: Indel
Location: chr3:93980427 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.92

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

Disease context

ARL13B-related disorder

Similar variants

ARL13B p.Phe2Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
ARL13B p.Phe2= Likely benign ★ same residue
ARL13B p.Leu211fs Likely pathogenic ★★ same condition
ARL13B p.Gln161Ter Likely pathogenic ★ same condition
ARL13B p.Lys225fs Likely pathogenic ★ same condition
ARL13B p.Lys350Ter Likely pathogenic ★ same condition
ARL13B p.Pro253fs Likely pathogenic ★ same condition
ARL13B c.*2C>T Likely benign 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-phe2fs (accessed [today's date]).

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