DNMBP p.Pro618=
c.1854G>A · VCV4084429
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0586%, 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 -2.4 | GERP -3.7 |
| Overall | ||
| CADD | 3.331 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0586%
African / African-American · 44/75,060 alleles
Filtering AF
0.0448%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.04%
Overall
0.00545%
88/1,614,158 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0586% | 1,706 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,167 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.0121% | 8,279 |
| Admixed American | 0.005% | 20,008 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- DNMBP
- Protein
- p.Pro618=
- Coding
- c.1854G>A
- MANE Select
- NM_015221
- Type
- single nucleotide variant
- Location
- chr10:99955620 (GRCh38)
- Gene constraint
- LOEUF 0.664 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.91 · 7 PDB
- Residue 618
- the 'disordered' region; a UniProt-annotated variant site (in ctrct48)
Similar variants
- DNMBP p.Arg1326His Uncertain significance ★★ ⚠ same type
- DNMBP p.Asn1560Lys Uncertain significance ★★ ⚠ same type
- DNMBP p.Ser984Cys Uncertain significance ★★ ⚠ same type
- DNMBP c.2554+8C>T Benign/Likely benign ★★ same type
- DNMBP c.3156+7A>G Benign ★★ same type
- DNMBP p.Asn373Lys Benign ★★ same type
- DNMBP p.Asn961= Benign ★★ same type
- DNMBP p.Cys1413Trp 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/dnmbp-p-pro618 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown