NCDN p.Pro681=
c.2043C>T · rs55743884 · VCV1694507
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.31%, nfe)
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 -8.6 | GERP -3.7 |
| Overall | ||
| CADD | 6.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.31%
European (non-Finnish) · 15,175/1,162,080 alleles
Filtering AF
1.29%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.28%
Overall
1.1%
17,296/1,577,788 alleles · low-frequency
exomes 16,003/1,425,462 · genomes 1,293/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.31% | 77 |
| Finnishnot grpmax-eligible | 1.15% | 87 |
| Remaining individualsnot grpmax-eligible | 1.04% | 96 |
| Admixed American | 0.722% | 138 |
| Amishnot grpmax-eligible | 0.439% | 228 |
| South Asian | 0.255% | 392 |
| African / African-American | 0.18% | 554 |
| Middle Eastern | 0.167% | 600 |
| Ashkenazi Jewishnot grpmax-eligible | 0.124% | 804 |
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
- NCDN
- Protein
- p.Pro681=
- Coding
- c.2043C>T
- MANE Select
- NM_014284
- dbSNP
- rs55743884
- Type
- single nucleotide variant
- Location
- chr1:35565516 (GRCh38)
- Gene constraint
- LOEUF 0.261 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 88.12
Similar variants
- NCDN p.Arg259Trp Uncertain significance ★★ ⚠ same type
- NCDN p.Arg423His Uncertain significance ★★ ⚠ same type
- NCDN p.Gly164Ser Uncertain significance ★★ ⚠ same type
- NCDN p.Gly189Ser Uncertain significance ★★ ⚠ same type
- NCDN p.Arg478Gln Pathogenic ★ ⚠ same type
- NCDN p.Glu433Gln Likely pathogenic ★ ⚠ same type
- NCDN p.Pro533Leu Likely pathogenic ★ same type
- NCDN p.Pro652Leu Pathogenic ★ 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/ncdn-p-pro681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown