Is AHI1 p.Arg596= (c.1788T>C) pathogenic?

AHI1 p.Arg596= (c.1788T>C) is classified Conflicting classifications of pathogenicity in AHI1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0225%, nfe); Associated with Joubert syndrome 3.

What condition is associated with AHI1 p.Arg596= (c.1788T>C)?

AHI1 p.Arg596= (c.1788T>C) is associated with Joubert syndrome 3, Joubert syndrome (ClinVar).

How common is AHI1 p.Arg596= (c.1788T>C) in the general population?

AHI1 p.Arg596= (c.1788T>C) is ultra-rare (popmax 0.0225%, nfe) (gnomAD).

AHI1 p.Arg596=

c.1788T>C · rs548478362 · VCV355506

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0225%, nfe)

Conditions

Joubert syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -5.7, phastCons 1
Overall
CADD	7.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0225% European (non-Finnish) · 265/1,176,406 alleles

Filtering AF 0.0203% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0194%

Overall 0.0169% 271/1,604,694 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0225%	4,439
Remaining individualsnot grpmax-eligible	0.00966%	10,349

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.Arg596=
Coding: c.1788T>C
MANE Select: NM_001134831
dbSNP: rs548478362
Type: single nucleotide variant
Location: chr6:135442706 (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 596: a UniProt-annotated variant site (in jbts3)

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

Also linked: Joubert syndrome

Similar variants

AHI1 p.Arg596Cys Uncertain significance ★★ ⚠ same residue
AHI1 p.Arg596His Uncertain significance ★ ⚠ same residue
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
AHI1 c.1779+1G>T Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.2492+1G>A Pathogenic/Likely pathogenic ★★ same condition
AHI1 c.2493-2A>G 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-arg596 (accessed [today's date]).

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