NCKAP1 p.Pro176=
c.528A>G · rs148713736 · VCV3034627
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.215%, afr)
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 1.4 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 9.811 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.215%
African / African-American · 161/75,026 alleles
Filtering AF
0.188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.177%
Overall
0.0117%
189/1,613,762 alleles · rare
exomes 106/1,461,524 · genomes 83/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.215% | 466 |
| Middle Eastern | 0.0165% | 6,058 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| Admixed American | 0.00667% | 15,000 |
| European (non-Finnish) | 0.00144% | 69,401 |
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
- NCKAP1
- Protein
- p.Pro176=
- Coding
- c.528A>G
- MANE Select
- NM_013436
- dbSNP
- rs148713736
- Type
- single nucleotide variant
- Location
- chr2:183002028 (GRCh38)
- Gene constraint
- LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.75 · 5 PDB
- Residue 176
- an α-helix
Similar variants
- NCKAP1 p.Pro176Ala Uncertain significance ★ ⚠ same residue
- NCKAP1 p.Arg798Ter Pathogenic ★★ same type
- NCKAP1 p.Ala1128Val Uncertain significance ★★ ⚠ same type
- NCKAP1 p.Arg1054His Uncertain significance ★★ ⚠ same type
- NCKAP1 p.Cys327Arg Uncertain significance ★★ ⚠ same type
- NCKAP1 p.Glu15Gly Uncertain significance ★★ ⚠ same type
- NCKAP1 p.Ile689Val Uncertain significance ★★ ⚠ same type
- NCKAP1 p.Leu268Phe 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/nckap1-p-pro176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown