NECTIN4 p.Lys49=
c.147A>G · VCV3633274
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
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 0.65 | GERP -2.1, phastCons 0.99 |
| Overall | ||
| CADD | 7.506 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/60,002 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.0131%
211/1,613,618 alleles · ultra-rare
exomes 191/1,461,424 · genomes 20/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,727 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,680 |
| Middle Eastern | 0.0164% | 6,084 |
| European (non-Finnish) | 0.0147% | 6,820 |
| African / African-American | 0.00534% | 18,732 |
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.Lys49=
- Coding
- c.147A>G
- MANE Select
- NM_030916
- Type
- single nucleotide variant
- Location
- chr1:161079882 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 79.79 · 5 PDB
- Residue 49
- a β-strand; the ig-like v-type domain
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-lys49 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown