NCKAP1L p.Ala331=
c.993A>G · rs145815142 · VCV2058761
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.299%, afr)
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 -4.2 | GERP -5.1 |
| Overall | ||
| CADD | 1.457 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.299%
African / African-American · 224/75,012 alleles
Filtering AF
0.267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.254%
Overall
0.0179%
289/1,613,986 alleles · rare
exomes 152/1,461,742 · genomes 137/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.299% | 335 |
| Admixed American | 0.04% | 2,501 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00659% | 15,180 |
| European (non-Finnish) | 0.000848% | 117,991 |
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.Ala331=
- Coding
- c.993A>G
- MANE Select
- NM_005337
- dbSNP
- rs145815142
- Type
- single nucleotide variant
- Location
- chr12:54516290 (GRCh38)
- Gene constraint
- LOEUF 0.46 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 92.83
Similar variants
- NCKAP1L p.Ala331Thr Uncertain significance ★ ⚠ same residue
- 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
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-ala331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown