Is AHI1 p.Ser389Ter (c.1166C>G) pathogenic?

AHI1 p.Ser389Ter (c.1166C>G) is classified Pathogenic/Likely pathogenic in AHI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-19). Very rare (popmax 0.00504%, nfe); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Ser389Ter (c.1166C>G)?

AHI1 p.Ser389Ter (c.1166C>G) is associated with Joubert syndrome, Joubert syndrome 3 (ClinVar).

How common is AHI1 p.Ser389Ter (c.1166C>G) in the general population?

AHI1 p.Ser389Ter (c.1166C>G) is very rare (popmax 0.00504%, nfe) (gnomAD).

AHI1 p.Ser389Ter

c.1166C>G · rs761388040 · VCV1073454

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00504%, nfe)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 29
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.7, phastCons 1
Overall
CADD	39.0	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 0.00504% European (non-Finnish) · 56/1,110,460 alleles

Filtering AF 0.00398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00358%

Overall 0.00433% 58/1,339,834 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00504%	19,830
Remaining individualsnot grpmax-eligible	0.00175%	56,994
African / African-American	0.00138%	72,312

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.Ser389Ter
Coding: c.1166C>G
MANE Select: NM_001134831
dbSNP: rs761388040
Type: single nucleotide variant
Location: chr6:135455912 (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 389: the 'interaction with hap1' region

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

Also linked: Joubert syndrome 3

Similar variants

AHI1 p.Ser389= Likely benign ★ same residue
AHI1 p.Ser389fs Pathogenic ★ 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-ser389ter (accessed [today's date]).

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