DCHS2 p.Ser688=
c.2064T>C · rs757694579 · VCV2655141
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -20 | GERP -4.5 |
| Overall | ||
| CADD | 0.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,070 alleles
Filtering AF
0.0024%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00285%
46/1,611,832 alleles · ultra-rare
exomes 42/1,459,662 · genomes 4/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,070 |
| East Asian | 0.00669% | 14,951 |
| African / African-American | 0.00534% | 18,717 |
| European (non-Finnish) | 0.00322% | 31,020 |
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.Ser688=
- Coding
- c.2064T>C
- MANE Select
- NM_001358235
- dbSNP
- rs757694579
- Type
- single nucleotide variant
- Location
- chr4:154377433 (GRCh38)
- Gene constraint
- LOEUF 0.909 · pLI <0.01 (gnomAD)
- Residue 688
- the cadherin 6 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-ser688 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown