DNAH1 p.Pro3563=
c.10689G>A · rs551397999 · VCV1597846
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
2
spermatogenic failure 18
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 -4.1 | GERP -3.2 |
| Overall | ||
| CADD | 4.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00622%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00403%
65/1,614,010 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| African / African-American | 0.012% | 8,340 |
| South Asian | 0.00659% | 15,181 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| European (non-Finnish) | 0.00373% | 26,815 |
| Finnishnot grpmax-eligible | 0.00312% | 32,015 |
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
- DNAH1
- Protein
- p.Pro3563=
- Coding
- c.10689G>A
- MANE Select
- NM_015512
- dbSNP
- rs551397999
- Type
- single nucleotide variant
- Location
- chr3:52394527 (GRCh38)
- Gene constraint
- LOEUF 0.759 · pLI <0.01 (gnomAD)
- Residue 3563
- a UniProt-annotated variant site (in spgf18)
Similar variants
- DNAH1 p.Pro3563Leu Uncertain significance ★ ⚠ same residue
- DNAH1 c.1034-2A>G Likely pathogenic ★★ same condition
- DNAH1 c.10474+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DNAH1 c.10968+2C>T Likely pathogenic ★★ same condition
- DNAH1 c.5244+1G>A Likely pathogenic ★★ same condition
- DNAH1 p.Arg1702Ter Pathogenic ★★ same condition
- DNAH1 p.Arg2479Ter Pathogenic/Likely pathogenic ★★ same condition
- DNAH1 p.Arg2622Ter 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/dnah1-p-pro3563 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown