NDE1 p.Pro247=
c.741T>G · rs138534309 · VCV159017
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.032%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -4.6 |
| Overall | ||
| CADD | 1.355 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.032%
African / African-American · 24/74,908 alleles
Filtering AF
0.022%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.00223%
36/1,613,164 alleles · ultra-rare
exomes 16/1,461,004 · genomes 20/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.032% | 3,121 |
| Admixed American | 0.0133% | 7,499 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,598 |
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
- NDE1
- Protein
- p.Pro247=
- Coding
- c.741T>G
- MANE Select
- NM_017668
- dbSNP
- rs138534309
- Type
- single nucleotide variant
- Location
- chr16:15694202 (GRCh38)
- Gene constraint
- LOEUF 0.851 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 78.40 · 1 PDB
- Residue 247
- the 'interaction with cenpf' region
Similar variants
- NDE1 p.Pro247Arg Uncertain significance ★ ⚠ same residue
- NDE1 p.Arg220Ter Pathogenic/Likely pathogenic ★★ same type
- NDE1 p.Arg37Ter Pathogenic ★★ same type
- MYH11 c.4578+6T>C Uncertain significance ★★ same type
- MYH11 c.4791+5G>A Uncertain significance ★★ same type
- MYH11 c.4954-3C>G Uncertain significance ★★ same type
- MYH11 c.5787-4685C>T Uncertain significance ★★ same type
- MYH11 p.Ala1311Glu 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/nde1-p-pro247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown