Is AHI1 p.Arg235fs (c.703dup) pathogenic?

AHI1 p.Arg235fs (c.703dup) is classified Pathogenic/Likely pathogenic in AHI1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-22). Very rare (popmax 0.00233%, nfe); Associated with AHI1-related disorder.

What condition is associated with AHI1 p.Arg235fs (c.703dup)?

AHI1 p.Arg235fs (c.703dup) is associated with AHI1-related disorder, Joubert syndrome 3, Joubert syndrome (ClinVar).

How common is AHI1 p.Arg235fs (c.703dup) in the general population?

AHI1 p.Arg235fs (c.703dup) is very rare (popmax 0.00233%, nfe) (gnomAD).

AHI1 p.Arg235fs

c.703dup · rs1336317768 · VCV847622

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00233%, nfe)

Conditions

AHI1-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 7 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -0.67
Overall
CADD	19.24	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00233% European (non-Finnish) · 26/1,116,872 alleles

Filtering AF 0.00162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00138%

Overall 0.00183% 27/1,477,230 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00233%	42,957
Remaining individualsnot grpmax-eligible	0.00177%	56,354

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: AHI1
Protein: p.Arg235fs
Coding: c.703dup
MANE Select: NM_001134831
dbSNP: rs1336317768
Type: Duplication
Location: chr6:135465859 (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 235: the 'interaction with hap1' region; the 'disordered' region

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

Disease context

AHI1-related disorder

Also linked: Joubert syndrome 3 Joubert syndrome

Similar variants

AHI1 p.Asn1020fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Cys614fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Leu33fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Leu37fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Leu413fs Pathogenic ★★ same condition
AHI1 p.Leu750fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Pro1102fs Pathogenic/Likely pathogenic ★★ same condition
AHI1 p.Thr304fs 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-arg235fs (accessed [today's date]).

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