NECTIN4 p.Ala7=
c.21C>T · rs377146825 · VCV2722372
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 6.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 14.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,884 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00199%
32/1,610,516 alleles · ultra-rare
exomes 29/1,458,560 · genomes 3/151,956 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,481 |
| European (non-Finnish) | 0.00203% | 49,165 |
| Admixed American | 0.00167% | 59,994 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,446 |
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.Ala7=
- Coding
- c.21C>T
- MANE Select
- NM_030916
- dbSNP
- rs377146825
- Type
- single nucleotide variant
- Location
- chr1:161089276 (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-ala7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown