NEDD4 p.Pro287=
c.861G>A · rs745912672 · VCV738174
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.034 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -7.5 |
| Overall | ||
| CADD | 9.869 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/74,906 alleles
Filtering AF
0.00922%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00803%
Overall
0.00849%
137/1,613,954 alleles · ultra-rare
exomes 130/1,461,824 · genomes 7/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,242 |
| European (non-Finnish) | 0.0101% | 9,916 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| Admixed American | 0.00167% | 59,992 |
| South Asian | 0.0011% | 91,082 |
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
- NEDD4
- Protein
- p.Pro287=
- Coding
- c.861G>A
- MANE Select
- NM_006154
- dbSNP
- rs745912672
- Type
- single nucleotide variant
- Location
- chr15:55860506 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.86 · 15 PDB
Similar variants
- NEDD4 p.Arg548His Uncertain significance ★★ ⚠ same type
- NEDD4 c.1484-6C>T Likely benign ★★ same type
- NEDD4 c.291+7901C>A Benign/Likely benign ★★ same type
- NEDD4 c.291+7911A>G Benign ★★ same type
- NEDD4 c.291+8022G>C Likely benign ★★ same type
- NEDD4 c.291+8368T>A Benign/Likely benign ★★ same type
- NEDD4 c.291+8666G>A Benign ★★ same type
- NEDD4 c.291+8732T>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/nedd4-p-pro287 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown