NECTIN4 p.Val451=
c.1353G>A · rs139594365 · VCV2060471
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.445%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.37 | gain · loss 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 10.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.445%
Middle Eastern · 27/6,062 alleles
Filtering AF
0.314%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.27%
Overall
0.0481%
776/1,614,210 alleles · rare
exomes 721/1,461,862 · genomes 55/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.445% | 225 |
| South Asian | 0.187% | 536 |
| European (non-Finnish) | 0.0459% | 2,177 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Admixed American | 0.015% | 6,669 |
| African / African-American | 0.00799% | 12,510 |
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
- NECTIN4
- Protein
- p.Val451=
- Coding
- c.1353G>A
- MANE Select
- NM_030916
- dbSNP
- rs139594365
- Type
- single nucleotide variant
- Location
- chr1:161072841 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 79.79 · 5 PDB
Similar variants
- NECTIN4 p.Asn489Asp Uncertain significance ★★ ⚠ same type
- NECTIN4 p.Glu8Lys Uncertain significance ★★ ⚠ same type
- NECTIN4 p.Met436Val Uncertain significance ★★ ⚠ same type
- NECTIN4 p.Pro463Ala Uncertain significance ★★ ⚠ same type
- NECTIN4 p.Thr497Met Uncertain significance ★★ ⚠ same type
- NECTIN4 c.1000+18A>G Benign ★★ same type
- NECTIN4 p.Arg284= Benign/Likely benign ★★ same type
- NECTIN4 p.Cys127= Likely 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/nectin4-p-val451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown