DNAH2 p.Ile3521=
c.10563T>C · rs139564557 · VCV2647387
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.176%, afr)
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 -5.1 | GERP -3.7 |
| Overall | ||
| CADD | 0.467 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.176%
African / African-American · 132/75,020 alleles
Filtering AF
0.152%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.142%
Overall
0.00867%
140/1,613,992 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.176% | 568 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,501 |
| European (non-Finnish) | 0.000254% | 393,331 |
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.Ile3521=
- Coding
- c.10563T>C
- MANE Select
- NM_020877
- dbSNP
- rs139564557
- Type
- single nucleotide variant
- Location
- chr17:7818669 (GRCh38)
- Gene constraint
- LOEUF 0.655 · pLI <0.01 (gnomAD)
- Residue 3521
- the 'aaa 5' region
Similar variants
- DNAH2 p.Ile3521Thr Uncertain significance ★ ⚠ same residue
- DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same type
- DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same type
- DNAH2 p.Arg2538Gln Uncertain significance ★★ same type
- DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same type
- DNAH2 p.Gln2069Glu Uncertain significance ★★ same type
- DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same type
- DNAH2 p.Pro3819Leu 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/dnah2-p-ile3521 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown