AHI1 p.Pro332=
c.996G>A · rs765587432 · VCV1077209
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Conditions
1
Joubert syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.053 | GERP -0.92, phastCons 0.008 |
| Overall | ||
| CADD | 8.609 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.00211%
34/1,613,738 alleles · ultra-rare
exomes 31/1,461,650 · genomes 3/152,088 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.01% | 10,001 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,801 |
| South Asian | 0.00439% | 22,771 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,230 |
| African / African-American | 0.00267% | 37,444 |
| East Asian | 0.00223% | 44,870 |
| European (non-Finnish) | 0.00136% | 73,740 |
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.Pro332=
- Coding
- c.996G>A
- MANE Select
- NM_001134831
- dbSNP
- rs765587432
- Type
- single nucleotide variant
- Location
- chr6:135457649 (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 332
- the 'interaction with hap1' region
Similar variants
- AHI1 p.Pro332Leu 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.2623+1G>A Pathogenic ★★ same condition
- AHI1 c.2623+1G>T 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-pro332 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown