DNAH2 p.Ser4012=
c.12036C>T · rs61744634 · VCV774929
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.773%, nfe)
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 -4.7 | GERP -3.7 |
| Overall | ||
| CADD | 2.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.773%
European (non-Finnish) · 9,119/1,179,980 alleles
Filtering AF
0.759%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.754%
Overall
0.619%
9,995/1,614,082 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.773% | 129 |
| Remaining individualsnot grpmax-eligible | 0.555% | 180 |
| Admixed American | 0.343% | 291 |
| Finnishnot grpmax-eligible | 0.287% | 348 |
| African / African-American | 0.135% | 743 |
| Middle Eastern | 0.0495% | 2,021 |
| East Asian | 0.0267% | 3,741 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0236% | 4,229 |
| South Asian | 0.0176% | 5,692 |
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.Ser4012=
- Coding
- c.12036C>T
- MANE Select
- NM_020877
- dbSNP
- rs61744634
- Type
- single nucleotide variant
- Location
- chr17:7830482 (GRCh38)
- Gene constraint
- LOEUF 0.655 · pLI <0.01 (gnomAD)
- Residue 4012
- the 'aaa 6' region; a UniProt-annotated variant site (in spgf45; decreased protein abundance; loss of inner dynein arm assembly; in spermatozoa from patients)
Similar variants
- 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
- DNAH2 c.10169+3G>A Benign ★★ 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-ser4012 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown