NCAPH p.Ala657=
c.1971G>A · rs149403246 · VCV730784
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0684%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.003 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.092 | GERP -3.4, phastCons 0.001 |
| Overall | ||
| CADD | 7.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0684%
Admixed American · 41/59,976 alleles
Filtering AF
0.0518%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0459%
Overall
0.0168%
271/1,613,200 alleles · ultra-rare
exomes 259/1,460,992 · genomes 12/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0684% | 1,463 |
| European (non-Finnish) | 0.0188% | 5,313 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,813 |
| East Asian | 0.00223% | 44,870 |
| South Asian | 0.0022% | 45,524 |
| Finnishnot grpmax-eligible | 0.00156% | 63,966 |
| African / African-American | 0.00133% | 74,918 |
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
- NCAPH
- Protein
- p.Ala657=
- Coding
- c.1971G>A
- MANE Select
- NM_015341
- dbSNP
- rs149403246
- Type
- single nucleotide variant
- Location
- chr2:96367346 (GRCh38)
- Gene constraint
- LOEUF 0.566 · pLI 0.11 (gnomAD)
- Structure
- AlphaFold pLDDT 60.16 · 1 PDB
Similar variants
- NCAPH p.Arg451Cys Uncertain significance ★★ ⚠ same type
- NCAPH c.1002+9A>G Benign/Likely benign ★★ same type
- NCAPH p.Arg221Gly Benign ★★ same type
- NCAPH p.Asp377= Benign ★★ same type
- NCAPH p.Val384Ile Benign/Likely benign ★★ same type
- NCAPH p.Val539Ala Benign ★★ same type
- NCAPH c.19+1G>C Likely pathogenic ★ same type
- NCAPH p.Ala198Pro 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/ncaph-p-ala657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown