DCHS1 p.Phe2134=
c.6402C>T · rs755974939 · VCV2641563
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 0.9 | GERP -3, phastCons 0.98 |
| Overall | ||
| CADD | 2.732 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,950 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.00093%
15/1,613,472 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,950 |
| African / African-American | 0.00133% | 74,924 |
| South Asian | 0.0011% | 90,998 |
| European (non-Finnish) | 0.00102% | 98,310 |
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.Phe2134=
- Coding
- c.6402C>T
- MANE Select
- NM_003737
- dbSNP
- rs755974939
- Type
- single nucleotide variant
- Location
- chr11:6626343 (GRCh38)
- Gene constraint
- LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
- Residue 2134
- the cadherin 20 domain
Similar variants
- 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
- DCHS1 p.Ala1454Val Uncertain significance ★★ ⚠ same type
- DCHS1 p.Ala1460Pro Uncertain significance ★★ same type
- DCHS1 p.Ala1490Glu 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-phe2134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown