NECTIN4 p.Pro149=
c.447C>T · rs761265853 · VCV2715592
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0823%, mid)
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 -0.041 | GERP -0.45, phastCons 0.21 |
| Overall | ||
| CADD | 7.346 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0823%
Middle Eastern · 5/6,074 alleles
Filtering AF
0.0324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00541%
87/1,607,384 alleles · ultra-rare
exomes 81/1,455,252 · genomes 6/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0823% | 1,215 |
| South Asian | 0.0286% | 3,501 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,482 |
| African / African-American | 0.00668% | 14,978 |
| European (non-Finnish) | 0.00373% | 26,807 |
| Admixed American | 0.00333% | 29,990 |
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.Pro149=
- Coding
- c.447C>T
- MANE Select
- NM_030916
- dbSNP
- rs761265853
- Type
- single nucleotide variant
- Location
- chr1:161077736 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.86 (gnomAD)
- Structure
- AlphaFold pLDDT 79.79 · 5 PDB
- Residue 149
- an α-helix; the ig-like c2-type 1 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-pro149 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown