ROGDI p.Leu89=
c.267G>A · rs770605828 · VCV1141099
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00117%, sas)
Conditions
1
amelocerebrohypohidrotic 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 0.88 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 7.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00117%
South Asian · 1/85,296 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000212%
3/1,415,470 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00117% | 85,296 |
| European (non-Finnish) | 0.000173% | 577,801 |
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
- ROGDI
- Protein
- p.Leu89=
- Coding
- c.267G>A
- MANE Select
- NM_024589
- dbSNP
- rs770605828
- Type
- single nucleotide variant
- Location
- chr16:4800567 (GRCh38)
- Gene constraint
- LOEUF 1.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.59 · 2 PDB
- Residue 89
- a β-strand
Similar variants
- ROGDI p.Leu89Met Uncertain significance ★ ⚠ same residue
- ROGDI c.117+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ROGDI c.46-2A>G Likely pathogenic ★★ same condition
- ROGDI c.531+5G>C Likely pathogenic ★★ same condition
- ROGDI c.645+2T>A Likely pathogenic ★★ same condition
- ROGDI p.Arg157Ter Pathogenic ★★ same condition
- ROGDI p.Gln112Ter Pathogenic/Likely pathogenic ★★ same condition
- ROGDI p.Gln114Ter 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/rogdi-p-leu89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown