DNAH8 p.Pro36Ser
c.106C>T · rs1178576726 · VCV525233
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, mid)
Conditions
2
spermatogenic failure 46
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.104 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.39 | GERP -4.7 |
| Regional constraint | o/e 1.12 | unconstrained · MANE · 19 kb · p 0.008 · regional, not allelic |
| Overall | ||
| CADD | 0.801 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,076 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.000372%
6/1,612,300 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,025 |
| African / African-American | 0.004% | 24,971 |
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
- DNAH8
- Protein
- p.Pro36Ser
- Coding
- c.106C>T
- MANE Select
- NM_001206927
- dbSNP
- rs1178576726
- Type
- single nucleotide variant
- Location
- chr6:38722915 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
Similar variants
- DNAH8 p.Pro36= Likely benign ★ same residue
- DNAH8 p.Pro36Thr Uncertain significance ★ same residue
- DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
- DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
- DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
- DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
- DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
- DNAH8 p.Arg207Ter 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/dnah8-p-pro36ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown