Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 29.8%, eas) — 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -5.5 |
| Overall | ||
| CADD | 1.037 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
29.8%
East Asian · 13,339/44,836 alleles
Filtering AF
29.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 29.2%
Overall
6.79%
109,554/1,613,430 alleles · common
exomes 90,601/1,461,288 · genomes 18,953/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 29.8% | 3 |
| Admixed American | 29.4% | 3 |
| African / African-American | 23.3% | 4 |
| South Asian | 13.5% | 7 |
| Remaining individualsnot grpmax-eligible | 8.2% | 12 |
| Middle Eastern | 7.93% | 13 |
| Finnishnot grpmax-eligible | 5.92% | 17 |
| European (non-Finnish) | 3.29% | 30 |
| Ashkenazi Jewishnot grpmax-eligible | 2.12% | 47 |
| Amishnot grpmax-eligible | 0.658% | 152 |
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
- DNAH11
- Protein
- p.Pro355=
- Coding
- c.1065A>G
- MANE Select
- NM_001277115
- dbSNP
- rs4392792
- Type
- single nucleotide variant
- Location
- chr7:21564268 (GRCh38)
- Gene constraint
- LOEUF 0.912 · pLI <0.01 (gnomAD)
- Residue 355
- the 'stem' region
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
- DNAH11 p.Pro355Leu Uncertain significance ★ ⚠ same residue
- DNAH11 c.10166-1G>C Likely pathogenic ★★ same condition
- DNAH11 c.10569-2A>G Likely pathogenic ★★ same condition
- DNAH11 c.10691+1G>T Pathogenic/Likely pathogenic ★★ same condition
- DNAH11 c.10896+1G>T Pathogenic/Likely pathogenic ★★ same condition
- DNAH11 c.11203-1G>C Pathogenic/Likely pathogenic ★★ same condition
- DNAH11 c.11839+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DNAH11 c.12934-1G>T 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/dnah11-p-pro355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown