Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.42%, eas)
Conditions
2
Joubert syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.474 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.35 | GERP -4.2 |
| Overall | ||
| CADD | 2.242 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.42%
East Asian · 1,980/44,804 alleles
Filtering AF
4.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.19%
Overall
2.11%
34,121/1,613,536 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.42% | 23 |
| South Asian | 4.11% | 24 |
| African / African-American | 3.57% | 28 |
| Remaining individualsnot grpmax-eligible | 2.66% | 38 |
| Finnishnot grpmax-eligible | 1.94% | 51 |
| Ashkenazi Jewishnot grpmax-eligible | 1.84% | 54 |
| European (non-Finnish) | 1.82% | 55 |
| Middle Eastern | 1.54% | 65 |
| Admixed American | 1.24% | 80 |
| Amishnot grpmax-eligible | 0.11% | 912 |
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.Asp741=
- Coding
- c.2223T>C
- MANE Select
- NM_001134831
- dbSNP
- rs2273761
- Type
- single nucleotide variant
- Location
- chr6:135433070 (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 741
- a UniProt-annotated variant site (in jbts3)
Similar variants
- AHI1 p.Asp741Gly 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
- 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-asp741 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown