CNP p.His126=
c.378C>T · rs112899212 · VCV2647778
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.198%, mid)
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 -8.2 | GERP -5.1 |
| Overall | ||
| CADD | 2.444 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.198%
Middle Eastern · 12/6,062 alleles
Filtering AF
0.126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.124%
Overall
0.118%
1,903/1,614,160 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.198% | 505 |
| European (non-Finnish) | 0.132% | 759 |
| Ashkenazi Jewishnot grpmax-eligible | 0.128% | 779 |
| South Asian | 0.123% | 813 |
| Finnishnot grpmax-eligible | 0.112% | 889 |
| Remaining individualsnot grpmax-eligible | 0.102% | 977 |
| Admixed American | 0.0633% | 1,579 |
| African / African-American | 0.0173% | 5,772 |
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
- CNP
- Protein
- p.His126=
- Coding
- c.378C>T
- MANE Select
- NM_033133
- dbSNP
- rs112899212
- Type
- single nucleotide variant
- Location
- chr17:41968442 (GRCh38)
- Gene constraint
- LOEUF 0.379 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 87.54 · 1 PDB
Similar variants
- CNP p.Arg353Trp Uncertain significance ★★ ⚠ same type
- CNP p.Gly365= Benign ★★ same type
- CNP p.Ala218Val Uncertain significance ★ ⚠ same type
- CNP p.Ala269Val Uncertain significance ★ ⚠ same type
- CNP p.Ala281Val Uncertain significance ★ ⚠ same type
- CNP p.Ala92Thr Uncertain significance ★ ⚠ same type
- CNP p.Arg114Gln Uncertain significance ★ ⚠ same type
- CNP p.Arg128Gln 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/cnp-p-his126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown