CHD3 p.Pro85Leu
c.254C>T · VCV3491944
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0744%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.063 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.85 | GERP -0.4, phastCons 1 |
| Overall | ||
| CADD | 12.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0744%
South Asian · 16/21,494 alleles
Filtering AF
0.0466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.038%
Overall
0.00217%
21/965,902 alleles · ultra-rare
exomes 17/821,976 · genomes 4/143,926 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0744% | 1,343 |
| Remaining individualsnot grpmax-eligible | 0.00683% | 14,644 |
| African / African-American | 0.0018% | 55,584 |
| European (non-Finnish) | 0.000246% | 406,635 |
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
- CHD3
- Protein
- p.Pro85Leu
- Coding
- c.254C>T
- MANE Select
- NM_001005273 · reported on NM_001005271
- Type
- single nucleotide variant
- Location
- chr17:7885060 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.21
- Residue 85
- the 'disordered' region
Similar variants
- CHD3 p.Arg85Trp Uncertain significance ★ ⚠ same residue
- CHD3 p.Arg85Gly Uncertain significance ★ ⚠ same residue
- CHD3 p.Arg103Ter Pathogenic ★★ same condition
- CHD3 p.Arg1078Gln Pathogenic/Likely pathogenic ★★ same condition
- CHD3 p.Arg966Trp Pathogenic ★★ ⚠ same condition
- CHD3 p.Arg985Trp Pathogenic/Likely pathogenic ★★ same condition
- CHD3 p.Pro1918= Likely pathogenic ★★ same condition
- CHD3 p.Arg1266Trp Uncertain significance ★★ ⚠ 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/chd3-p-pro85leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown