Is AHI1 p.Pro64fs (c.188_189insC) pathogenic?

AHI1 p.Pro64fs (c.188189insC) is classified Likely pathogenic in AHI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). Associated with Joubert syndrome 3.

What condition is associated with AHI1 p.Pro64fs (c.188_189insC)?

AHI1 p.Pro64fs (c.188_189insC) is associated with Joubert syndrome 3 (ClinVar).

AHI1 p.Pro64fs

c.188_189insC · VCV3593193

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Joubert syndrome 3

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 6 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.4	GERP -3.2

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

Variant & gene context

Gene: AHI1
Protein: p.Pro64fs
Coding: c.188_189insC
MANE Select: NM_001134831
Type: Insertion
Location: chr6:135467581 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.03 · 1 PDB
Residue 64: the 'disordered' region

Full AHI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AHI1 p.Pro64His Uncertain significance ★★ ⚠ same residue
AHI1 c.1626+4_1626+5insTTAC Pathogenic ★ same condition
AHI1 p.Lys1167fs Likely pathogenic ★ same condition
AHI1 p.Pro64= Conflicting classifications of pathogenicity ★ same residue
AHI1 p.Asn790fs Pathogenic same condition
AHI1 c.1152-1G>A Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.1152-2A>G Pathogenic ★★ same condition
AHI1 c.1626+1G>A 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/ahi1-p-pro64fs (accessed [today's date]).

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