HYDIN p.Phe1622=
c.4866T>C · rs758028170 · VCV3026377
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0178%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -2.7, phastCons 0.004 |
| Overall | ||
| CADD | 1.865 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0178%
Middle Eastern · 1/5,608 alleles
Filtering AF
0.0019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00234%
36/1,540,666 alleles · ultra-rare
exomes 34/1,389,020 · genomes 2/151,646 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0178% | 5,608 |
| Remaining individualsnot grpmax-eligible | 0.00838% | 11,939 |
| European (non-Finnish) | 0.00267% | 37,414 |
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.Phe1622=
- Coding
- c.4866T>C
- MANE Select
- NM_001270974
- dbSNP
- rs758028170
- Type
- single nucleotide variant
- Location
- chr16:70974577 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI <0.01 (gnomAD)
- Residue 1622
- 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-phe1622 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown