DNAH2 p.Asp456Ala
c.1367A>C · rs145415467 · VCV2283933
Computational evidence
| Protein change | ||
| AlphaMissense | 0.299 | likely benign |
|---|---|---|
| REVEL | 0.26 | 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 11 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic |
| Overall | ||
| CADD | 25.8 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0707% | 1,415 |
| Admixed American | 0.00333% | 29,991 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 8.48e-05% | 1,179,906 |
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
- DNAH2
- Protein
- p.Asp456Ala
- Coding
- c.1367A>C
- MANE Select
- NM_020877
- dbSNP
- rs145415467
- Type
- single nucleotide variant
- Location
- chr17:7739929 (GRCh38)
- Gene constraint
- LOEUF 0.655 · pLI <0.01 (gnomAD)
- Residue 456
- the 'stem' region
Similar variants
- DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same condition
- DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
- DNAH2 p.Arg2538Gln Uncertain significance ★★ same condition
- DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same condition
- DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
- DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
- DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ same condition
- DNAH2 p.Ala1058Thr Benign/Likely benign ★★ 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/dnah2-p-asp456ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown