CHD7 p.Pro558=
c.1674G>A · rs763024481 · VCV1777761
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00499%, sas)
Conditions
2
Inborn genetic diseases
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 0.39 | GERP -4.3, phastCons 0.58 |
| Overall | ||
| CADD | 8.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00499%
South Asian · 4/80,166 alleles
Filtering AF
0.00167%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000985%
Overall
0.000926%
13/1,403,746 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00499% | 20,041 |
| East Asian | 0.00227% | 44,122 |
| Admixed American | 0.00209% | 47,810 |
| European (non-Finnish) | 0.000605% | 165,198 |
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
- CHD7
- Protein
- p.Pro558=
- Coding
- c.1674G>A
- MANE Select
- NM_017780
- dbSNP
- rs763024481
- Type
- single nucleotide variant
- Location
- chr8:60781008 (GRCh38)
- Gene constraint
- LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 558
- the 'disordered' region; a UniProt-annotated variant site (in charges; uncertain significance)
Similar variants
- CHD7 p.Pro558Ala Benign/Likely benign ★★ same residue
- CHD7 c.2097-2A>G Pathogenic ★★ same condition
- CHD7 c.2238+1G>A Pathogenic ★★ same condition
- CHD7 c.2377-1G>A Likely pathogenic ★★ same condition
- CHD7 c.2613+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD7 c.2836-1G>A Pathogenic/Likely pathogenic ★★ same condition
- CHD7 c.2836-2A>T Pathogenic ★★ same condition
- CHD7 c.2957+2T>C Pathogenic ★★ same condition
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/chd7-p-pro558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown