ROGDI p.Val74=
c.222G>C · rs2505727689 · VCV2126989
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000425%, nfe)
Conditions
1
amelocerebrohypohidrotic syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 13.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000425%
European (non-Finnish) · 5/1,176,656 alleles
Filtering AF
0.000125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.1e-05%
Overall
0.000343%
5/1,456,840 alleles · very rare
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.Val74=
- Coding
- c.222G>C
- MANE Select
- NM_024589
- dbSNP
- rs2505727689
- Type
- single nucleotide variant
- Location
- chr16:4801300 (GRCh38)
- Gene constraint
- LOEUF 1.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.59 · 2 PDB
- Residue 74
- a β-strand
Similar variants
- 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
- ROGDI p.Gln96Ter 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-val74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown