DNHD1 p.Val4000=
c.12000T>G · rs774560297 · VCV745615
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.04%, 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 -1.9 | GERP -1.4 |
| Overall | ||
| CADD | 0.233 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.04%
African / African-American · 30/74,948 alleles
Filtering AF
0.0288%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0249%
Overall
0.00273%
44/1,613,592 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.04% | 2,498 |
| Admixed American | 0.0167% | 5,992 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,820 |
| European (non-Finnish) | 8.48e-05% | 1,179,770 |
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
- DNHD1
- Protein
- p.Val4000=
- Coding
- c.12000T>G
- MANE Select
- NM_144666
- dbSNP
- rs774560297
- Type
- single nucleotide variant
- Location
- chr11:6567509 (GRCh38)
- Gene constraint
- LOEUF 0.897 · pLI <0.01 (gnomAD)
- Residue 4000
- a UniProt-annotated variant site (in spgf65); a UniProt-annotated variant site (in spgf65; low expression, if any, in sperm flagella)
Similar variants
- DNHD1 p.Val4000Ile Uncertain significance ★ ⚠ same residue
- DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
- DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
- DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
- DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ same type
- DNHD1 p.Tyr2166Ter Pathogenic/Likely pathogenic ★★ same type
- DNHD1 p.Arg1582Trp Uncertain significance ★★ same type
- DNHD1 p.Arg1873Ser 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/dnhd1-p-val4000 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown