NECTIN1 p.Arg466=
c.1398G>A · rs142388398 · VCV2724545
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.127%, 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 0.79 | GERP -0.53, phastCons 1 |
| Overall | ||
| CADD | 7.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.127%
African / African-American · 95/75,024 alleles
Filtering AF
0.106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0983%
Overall
0.00737%
119/1,613,984 alleles · rare
exomes 59/1,461,726 · genomes 60/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.127% | 790 |
| Admixed American | 0.02% | 5,001 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| European (non-Finnish) | 8.47e-05% | 1,179,952 |
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
- NECTIN1
- Protein
- p.Arg466=
- Coding
- c.1398G>A
- MANE Select
- NM_002855
- dbSNP
- rs142388398
- Type
- single nucleotide variant
- Location
- chr11:119664903 (GRCh38)
- Gene constraint
- LOEUF 0.659 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.80 · 6 PDB
- Residue 466
- a UniProt-annotated variant site (in edmi); a UniProt-annotated variant site (in edmi and ofc7); the 'disordered' region
Similar variants
- NECTIN1 c.*1139G>A Uncertain significance ★★ same type
- NECTIN1 c.*1179C>G Uncertain significance ★★ same type
- NECTIN1 c.*1595C>A Uncertain significance ★★ same type
- NECTIN1 c.*185T>C Uncertain significance ★★ same type
- NECTIN1 c.*2416A>G Uncertain significance ★★ same type
- NECTIN1 c.*3440G>A Uncertain significance ★★ same type
- NECTIN1 c.*3705G>A Uncertain significance ★★ same type
- NECTIN1 c.*607C>A 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/nectin1-p-arg466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown