HYDIN p.Pro1253=
c.3759C>T · VCV3904957
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.191%, afr)
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 -10 | GERP -3.5 |
| Overall | ||
| CADD | 0.066 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.191%
African / African-American · 143/74,938 alleles
Filtering AF
0.165%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.156%
Overall
0.011%
178/1,613,634 alleles · rare
exomes 91/1,461,546 · genomes 87/152,088 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.191% | 524 |
| Middle Eastern | 0.0165% | 6,060 |
| Admixed American | 0.0134% | 7,490 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,925 |
| South Asian | 0.00769% | 13,007 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,582 |
| European (non-Finnish) | 0.000932% | 107,259 |
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
- HYDIN
- Protein
- p.Pro1253=
- Coding
- c.3759C>T
- MANE Select
- NM_001270974
- Type
- single nucleotide variant
- Location
- chr16:70992096 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI <0.01 (gnomAD)
- Residue 1253
- a UniProt-annotated variant site (in cild5; uncertain significance)
Similar variants
- HYDIN c.12444-1G>A Likely pathogenic ★★ same type
- HYDIN c.12444-3C>G Likely pathogenic ★★ same type
- HYDIN c.6669+1G>A Likely pathogenic ★★ same type
- HYDIN p.Arg2120Ter Likely pathogenic ★★ same type
- HYDIN p.Arg444Ter Pathogenic/Likely pathogenic ★★ same type
- HYDIN p.Glu683Ter Pathogenic/Likely pathogenic ★★ same type
- HYDIN p.Tyr599Ter Pathogenic/Likely pathogenic ★★ same type
- HYDIN p.Arg163Gln Uncertain significance ★★ ⚠ same type
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/hydin-p-pro1253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown