DNAH3 p.Arg3658Lys
c.10973G>A · rs147732992 · VCV774340
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1844 | likely benign |
|---|---|---|
| REVEL | 0.21 | benign-leaning |
| ⇒ AlphaMissense and REVEL both call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 23.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R3704K vs ClinVar R3658K) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.55% | 64 |
| European (non-Finnish) | 0.978% | 102 |
| Remaining individualsnot grpmax-eligible | 0.754% | 133 |
| Admixed American | 0.723% | 138 |
| Amishnot grpmax-eligible | 0.439% | 228 |
| Ashkenazi Jewishnot grpmax-eligible | 0.193% | 519 |
| African / African-American | 0.189% | 528 |
| Finnishnot grpmax-eligible | 0.0969% | 1,032 |
| South Asian | 0.0351% | 2,846 |
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.Arg3658Lys
- Coding
- c.10973G>A
- MANE Select
- NM_001347886
- dbSNP
- rs147732992
- Type
- single nucleotide variant
- Location
- chr16:20952510 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Residue 3658
- the 'aaa 6' region; 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); a UniProt-annotated variant site (found in a male with oligoasthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; disorganization of the flagellar axoneme ultrastructure, including abnormalities in the inner dynein arms, mitochondrial sheath and fibrous sheath)
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-arg3658lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown