Is AHI1 p.Arg723= (c.2169G>T) pathogenic?

AHI1 p.Arg723= (c.2169G>T) is classified Likely benign in AHI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-20). Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with AHI1 p.Arg723= (c.2169G>T)?

AHI1 p.Arg723= (c.2169G>T) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Arg723= (c.2169G>T) in the general population?

AHI1 p.Arg723= (c.2169G>T) is absent from gnomAD v4.1 (gnomAD).

AHI1 p.Arg723=

c.2169G>T · rs2128022641 · VCV1615929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.035	moderately benign-leaning
Splicing
SpliceAI	Δ0.21	acceptor loss, 46 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.11	GERP -2.7, phastCons 0.002
Overall
CADD	7.014	PHRED · no single calibrated threshold — expert panels disagree

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: AHI1
Protein: p.Arg723=
Coding: c.2169G>T
MANE Select: NM_001134831
dbSNP: rs2128022641
Type: single nucleotide variant
Location: chr6:135433124 (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 723: a UniProt-annotated variant site (in jbts3); a UniProt-annotated variant site (in jbts3; loss of localization at the primary cilium; loss of positive modulation of classical wnt signaling; no effect on interaction with ctnnb1)

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

Disease context

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

Similar variants

AHI1 p.Arg723Gly Likely pathogenic ★ same residue
AHI1 p.Arg723Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
AHI1 p.Arg723Trp 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

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-arg723 (accessed [today's date]).

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