HYDIN p.Pro4493=
c.13479G>A · VCV3341551
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.76%, mid) — too common for a highly-penetrant pathogenic allele
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 -20 | GERP -3.1 |
| Overall | ||
| CADD | 0.035 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.76%
Middle Eastern · 529/6,038 alleles
Filtering AF
8.14%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.9%
Overall
1.09%
17,512/1,604,480 alleles · common
exomes 16,126/1,453,466 · genomes 1,386/151,014 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 8.76% | 11 |
| Ashkenazi Jewishnot grpmax-eligible | 3.62% | 28 |
| Amishnot grpmax-eligible | 2.53% | 39 |
| Remaining individualsnot grpmax-eligible | 1.36% | 74 |
| Admixed American | 1.22% | 82 |
| South Asian | 1.12% | 90 |
| European (non-Finnish) | 1.1% | 91 |
| Finnishnot grpmax-eligible | 0.307% | 326 |
| African / African-American | 0.228% | 438 |
| East Asian | 0.00671% | 14,893 |
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.Pro4493=
- Coding
- c.13479G>A
- MANE Select
- NM_001270974
- Type
- single nucleotide variant
- Location
- chr16:70834087 (GRCh38)
- Gene constraint
- LOEUF 0.555 · pLI <0.01 (gnomAD)
- Residue 4493
- a UniProt-annotated variant site (in cild5; uncertain significance); a UniProt-annotated variant site (in cild5; likely pathogenic; absence of spef2 in ciliary axonemes of respiratory cells)
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-pro4493 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown