CHCHD2 p.Pro15=
c.45G>C · rs760289183 · VCV2015448
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 | phastCons 1 |
| Overall | ||
| CADD | 14.89 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,938 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000186%
3/1,613,314 alleles · very rare
exomes 3/1,461,024 · genomes 0/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,969 |
| European (non-Finnish) | 8.48e-05% | 1,179,592 |
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
- CHCHD2
- Protein
- p.Pro15=
- Coding
- c.45G>C
- MANE Select
- NM_016139
- dbSNP
- rs760289183
- Type
- single nucleotide variant
- Location
- chr7:56106369 (GRCh38)
- Gene constraint
- LOEUF 1.586 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.86 · 2 PDB
- Residue 15
- the 'disordered' region
Similar variants
- CHCHD2 c.446-9T>A Uncertain significance ★★ same type
- CHCHD2 p.Ala32Thr Uncertain significance ★★ ⚠ same type
- CHCHD2 p.Ala60Val Uncertain significance ★★ ⚠ same type
- CHCHD2 p.Arg51Gln Uncertain significance ★★ ⚠ same type
- CHCHD2 p.Ile131Val Uncertain significance ★★ ⚠ same type
- CHCHD2 p.Pro34Leu Uncertain significance ★★ ⚠ same type
- CHCHD2 p.Pro39Thr Uncertain significance ★★ ⚠ same type
- CHCHD2 c.300+159T>G Benign ★★ 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/chchd2-p-pro15 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown