Is AHI1 p.Pro143= (c.429G>A) pathogenic?

AHI1 p.Pro143= (c.429G>A) is classified Likely benign in AHI1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). Ultra-rare (popmax 0.0164%, mid); Associated with Joubert syndrome.

What condition is associated with AHI1 p.Pro143= (c.429G>A)?

AHI1 p.Pro143= (c.429G>A) is associated with Joubert syndrome (ClinVar).

How common is AHI1 p.Pro143= (c.429G>A) in the general population?

AHI1 p.Pro143= (c.429G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

AHI1 p.Pro143=

c.429G>A · rs376566315 · VCV3021105

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -2.3
Overall
CADD	5.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00112% 18/1,613,638 alleles · ultra-rare exomes 16/1,461,554 · genomes 2/152,084 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
South Asian	0.00659%	15,178
Remaining individualsnot grpmax-eligible	0.0032%	31,229
Admixed American	0.00167%	59,960
European (non-Finnish)	0.000678%	147,476

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.Pro143=
Coding: c.429G>A
MANE Select: NM_001134831
dbSNP: rs376566315
Type: single nucleotide variant
Location: chr6:135466134 (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 143: the 'interaction with hap1' region; the 'disordered' 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

Similar variants

AHI1 p.Pro143Arg Likely benign ★★ same residue
AHI1 p.Pro143Leu Conflicting classifications of pathogenicity ★ ⚠ 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.2623+1G>A 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-pro143 (accessed [today's date]).

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