CHD3 p.Pro84Leu
c.251C>T · rs766660828 · VCV1049451
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.168%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.035 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 0.2, phastCons 0.98 |
| Overall | ||
| CADD | 11.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.168%
South Asian · 37/22,050 alleles
Filtering AF
0.125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.11%
Overall
0.0758%
757/998,964 alleles · rare
exomes 696/855,574 · genomes 61/143,390 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.168% | 596 |
| Middle Eastern | 0.101% | 991 |
| European (non-Finnish) | 0.0815% | 1,227 |
| Remaining individualsnot grpmax-eligible | 0.0622% | 1,607 |
| Finnishnot grpmax-eligible | 0.0377% | 2,654 |
| African / African-American | 0.0125% | 8,019 |
| Admixed American | 0.0124% | 8,089 |
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.Pro84Leu
- Coding
- c.251C>T
- MANE Select
- NM_001005273 · reported on NM_001005271
- dbSNP
- rs766660828
- Type
- single nucleotide variant
- Location
- chr17:7885057 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.21
- Residue 84
- the 'disordered' region
Similar variants
- CHD3 p.Pro84Thr Uncertain significance ★★ same residue
- CHD3 p.Pro84Ser 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-pro84leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown