DCHS1 p.Arg1229=
c.3687C>T · rs200997946 · VCV1595420
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0283%, amr)
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 -4.4 | GERP -3.8 |
| Overall | ||
| CADD | 0.376 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0283%
Admixed American · 17/60,032 alleles
Filtering AF
0.018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.0129%
209/1,613,976 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0283% | 3,531 |
| European (non-Finnish) | 0.0154% | 6,483 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| African / African-American | 0.00133% | 75,054 |
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
- DCHS1
- Protein
- p.Arg1229=
- Coding
- c.3687C>T
- MANE Select
- NM_003737
- dbSNP
- rs200997946
- Type
- single nucleotide variant
- Location
- chr11:6631396 (GRCh38)
- Gene constraint
- LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
- Residue 1229
- the cadherin 12 domain
Similar variants
- DCHS1 p.Arg1229Cys Uncertain significance ★★ ⚠ same residue
- DCHS1 p.Arg1229Leu Uncertain significance ★★ ⚠ same residue
- DCHS1 p.Arg1229His Conflicting classifications of pathogenicity ★ ⚠ same residue
- DCHS1 p.Arg2141Ter Pathogenic/Likely pathogenic ★★ same type
- DCHS1 p.Arg2330Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- DCHS1 p.Ala1241Val Uncertain significance ★★ same type
- DCHS1 p.Ala1325Ser Uncertain significance ★★ ⚠ same type
- DCHS1 p.Ala142Thr Uncertain significance ★★ ⚠ 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/dchs1-p-arg1229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown