CHCHD2 p.Pro26=
c.78C>T · rs753881759 · VCV2196911
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00674%, amr)
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 0.61 | phastCons 0.11 |
| Overall | ||
| CADD | 8.699 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00674%
Admixed American · 4/59,376 alleles
Filtering AF
0.00227%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.00149%
24/1,606,254 alleles · very rare
exomes 20/1,454,106 · genomes 4/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00674% | 14,844 |
| European (non-Finnish) | 0.00162% | 61,892 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,052 |
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.Pro26=
- Coding
- c.78C>T
- MANE Select
- NM_016139
- dbSNP
- rs753881759
- Type
- single nucleotide variant
- Location
- chr7:56104448 (GRCh38)
- Gene constraint
- LOEUF 1.586 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.86 · 2 PDB
- Residue 26
- 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-pro26 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown