NECTIN1 p.Ala351=
c.1053G>C · rs141063530 · VCV3045303
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0517%, nfe)
Conditions
1
NECTIN1-related disorder
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 -1.5 | GERP -3 |
| Overall | ||
| CADD | 5.656 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0517%
European (non-Finnish) · 610/1,179,928 alleles
Filtering AF
0.0483%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0469%
Overall
0.0397%
640/1,613,994 alleles · ultra-rare
exomes 607/1,461,682 · genomes 33/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0517% | 1,934 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Middle Eastern | 0.0165% | 6,060 |
| Admixed American | 0.0117% | 8,572 |
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.Ala351=
- Coding
- c.1053G>C
- MANE Select
- NM_002855 · reported on NM_203285
- dbSNP
- rs141063530
- Type
- single nucleotide variant
- Location
- chr11:119639963 (GRCh38)
- Gene constraint
- LOEUF 0.659 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.80 · 6 PDB
- Residue 351
- a UniProt-annotated variant site (in edmi); a UniProt-annotated variant site (in edmi and ofc7)
Disease context
NECTIN1-related disorder
Similar variants
- NECTIN1 p.Pro351= Likely benign ★ same residue
- NECTIN1 c.1003+534G>A Likely benign same condition
- NECTIN1 c.1003+557G>T Benign same condition
- NECTIN1 c.79+9G>A Likely benign same condition
- NECTIN1 p.Asp46= Likely benign same condition
- NECTIN1 p.Gln409= Likely benign same condition
- NECTIN1 p.Pro340= Likely benign same condition
- NECTIN1 p.Thr21= Likely benign same condition
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-ala351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown