Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 59.8%, sas) — 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 0.76 | GERP -5.4, phastCons 1 |
| Overall | ||
| CADD | 8.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
59.8%
South Asian · 54,470/91,064 alleles
Filtering AF
59.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 59.2%
Overall
47.1%
760,826/1,613,834 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 59.8% | 2 |
| African / African-American | 58.9% | 2 |
| Finnishnot grpmax-eligible | 49.5% | 2 |
| East Asian | 49.4% | 2 |
| Admixed American | 48.1% | 2 |
| Remaining individualsnot grpmax-eligible | 48.1% | 2 |
| European (non-Finnish) | 45.2% | 2 |
| Amishnot grpmax-eligible | 44.5% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 43.5% | 2 |
| Middle Eastern | 42.9% | 2 |
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
- DNAH3
- Protein
- p.Lys2126=
- Coding
- c.6378A>G
- MANE Select
- NM_001347886
- dbSNP
- rs3115446
- Type
- single nucleotide variant
- Location
- chr16:20997368 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Residue 2126
- a UniProt-annotated variant site (found in a male with oligoasthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; partial loss and disintegration of the flagellar axoneme, accompanied by damage to the mitochondrial sheath); a UniProt-annotated variant site (found in a male with asthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; disorganization of flagellar components, notably inner dynein arms); the 'aaa 3' region
Similar variants
- DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
- DNAH3 p.Arg1228Gln Uncertain significance ★★ same type
- DNAH3 p.Arg635Gln Uncertain significance ★★ same type
- DNAH3 p.Asn1728Ser Uncertain significance ★★ ⚠ same type
- DNAH3 p.Asp3656Asn Uncertain significance ★★ same type
- DNAH3 p.Leu2597Val Uncertain significance ★★ same type
- DNAH3 p.Leu4044Phe Uncertain significance ★★ ⚠ same type
- DNAH3 p.Lys374Gln 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/dnah3-p-lys2126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown