CHD3 p.Leu83Pro
c.248T>C · VCV3832779
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0336%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.034 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.55 | GERP 0.2, phastCons 0.002 |
| Overall | ||
| CADD | 9.647 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0336%
South Asian · 7/20,810 alleles
Filtering AF
0.0157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0111%
Overall
0.00512%
50/976,244 alleles · ultra-rare
exomes 43/852,090 · genomes 7/124,154 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0336% | 2,973 |
| Remaining individualsnot grpmax-eligible | 0.0197% | 5,065 |
| East Asian | 0.0106% | 9,472 |
| Finnishnot grpmax-eligible | 0.0102% | 9,844 |
| European (non-Finnish) | 0.00398% | 25,128 |
| African / African-American | 0.00395% | 25,290 |
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.Leu83Pro
- Coding
- c.248T>C
- MANE Select
- NM_001005273 · reported on NM_001005271
- Type
- single nucleotide variant
- Location
- chr17:7885054 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 63.21
- Residue 83
- the 'disordered' region
Similar variants
- 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
- CHD3 p.Arg1377Cys Uncertain significance ★★ ⚠ same condition
- CHD3 p.Arg1381Leu 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-leu83pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown