NCKAP1L p.Pro656=
c.1968C>T · rs117115909 · VCV2190017
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0197%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.7 | GERP -5.3 |
| Overall | ||
| CADD | 5.548 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0197%
European (non-Finnish) · 232/1,180,010 alleles
Filtering AF
0.0176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0168%
Overall
0.0149%
241/1,613,992 alleles · ultra-rare
exomes 234/1,461,842 · genomes 7/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0197% | 5,086 |
| Admixed American | 0.005% | 20,001 |
| East Asian | 0.00446% | 22,436 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| African / African-American | 0.00267% | 37,487 |
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
- NCKAP1L
- Protein
- p.Pro656=
- Coding
- c.1968C>T
- MANE Select
- NM_005337
- dbSNP
- rs117115909
- Type
- single nucleotide variant
- Location
- chr12:54523483 (GRCh38)
- Gene constraint
- LOEUF 0.46 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 92.83
- Residue 656
- the 'disordered' region
Similar variants
- NCKAP1L p.Met371Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- NCKAP1L p.Ala219Thr Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Ala760Val Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Arg28His Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Arg419Gln Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Arg546Cys Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Arg68Gln Uncertain significance ★★ ⚠ same type
- NCKAP1L p.Arg736Gln Uncertain significance ★★ ⚠ 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/nckap1l-p-pro656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown