DCHS2 p.Ser564=
c.1692C>A · rs374018766 · VCV2655142
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0157%, nfe)
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 -11 | GERP -4.5 |
| Overall | ||
| CADD | 0.076 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0157%
European (non-Finnish) · 180/1,146,964 alleles
Filtering AF
0.0138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0131%
Overall
0.012%
186/1,551,528 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0157% | 6,372 |
| Remaining individualsnot grpmax-eligible | 0.00499% | 20,031 |
| African / African-American | 0.00274% | 36,526 |
| Admixed American | 0.00196% | 50,984 |
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
- DCHS2
- Protein
- p.Ser564=
- Coding
- c.1692C>A
- MANE Select
- NM_001358235
- dbSNP
- rs374018766
- Type
- single nucleotide variant
- Location
- chr4:154489664 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Residue 564
- the cadherin 5 domain
Similar variants
- DCHS2 c.2053-13744T>A Uncertain significance ★ same type
- DCHS2 c.2053-13798T>C Uncertain significance ★ same type
- DCHS2 c.2053-13820G>A Uncertain significance ★ same type
- DCHS2 c.2053-13834C>G Uncertain significance ★ same type
- DCHS2 c.2244+3317A>T Uncertain significance ★ same type
- DCHS2 c.2476+8901A>C Uncertain significance ★ same type
- DCHS2 c.2477-1G>T Uncertain significance ★ same type
- DCHS2 c.3730+872C>T 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/dchs2-p-ser564 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown