Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 33.9%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
primary ciliary dyskinesia
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 -5 | GERP -3.7 |
| Overall | ||
| CADD | 0.635 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
33.9%
African / African-American · 25,283/74,684 alleles
Filtering AF
33.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 33.4%
Overall
2.1%
33,838/1,612,566 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 33.9% | 3 |
| Middle Eastern | 4.56% | 22 |
| Admixed American | 3.28% | 31 |
| Remaining individualsnot grpmax-eligible | 2.92% | 34 |
| Ashkenazi Jewishnot grpmax-eligible | 2.79% | 36 |
| South Asian | 0.293% | 342 |
| European (non-Finnish) | 0.287% | 348 |
| Finnishnot grpmax-eligible | 0.0141% | 7,101 |
| East Asian | 0.00446% | 22,423 |
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.Ala1847=
- Coding
- c.5541C>T
- MANE Select
- NM_001206927
- dbSNP
- rs1678746
- Type
- single nucleotide variant
- Location
- chr6:38852768 (GRCh38)
- Gene constraint
- LOEUF 0.692 · pLI <0.01 (gnomAD)
- Residue 1847
- the 'aaa 1' region; a binding site; a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance)
Disease context
primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Primary ciliary dyskinesia (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Neonatal
- Prevalence
- 1-5 / 10 000 (Pakistan)
Similar variants
- 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
- DNAH8 p.Arg2878Ter Pathogenic ★★ same condition
- DNAH8 p.Arg4166Ter 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-ala1847 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown