Is DCHS2 p.Ser562= (c.1686C>T) pathogenic?

DCHS2 p.Ser562= (c.1686C>T) is classified Benign in DCHS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 85.5%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DCHS2-related disorder.

What condition is associated with DCHS2 p.Ser562= (c.1686C>T)?

DCHS2 p.Ser562= (c.1686C>T) is associated with DCHS2-related disorder (ClinVar).

DCHS2 p.Ser562=

Q: How common is DCHS2 p.Ser562= (c.1686C>T) in the general population?

DCHS2 p.Ser562= (c.1686C>T) is common (popmax 85.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1686C>T · rs4696593 · VCV3059101

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 85.5%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

DCHS2-related disorder

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 1	GERP -1.4, phastCons 1
Overall
CADD	8.689	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 85.5% East Asian · 34,915/40,848 alleles

Filtering AF 84.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 84.4%

Overall 54.6% 846,860/1,551,340 alleles · common exomes 766,751/1,399,376 · genomes 80,109/151,964 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	85.5%	1
Finnishnot grpmax-eligible	59.5%	2
Ashkenazi Jewishnot grpmax-eligible	55.4%	2
South Asian	54.8%	2
Remaining individualsnot grpmax-eligible	54.4%	2
European (non-Finnish)	54%	2
Amishnot grpmax-eligible	53.7%	2
Middle Eastern	50.7%	2
Admixed American	49.7%	2
African / African-American	45.9%	2

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.Ser562=
Coding: c.1686C>T
MANE Select: NM_001358235
dbSNP: rs4696593
Type: single nucleotide variant
Location: chr4:154489670 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Residue 562: the cadherin 5 domain

Full DCHS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DCHS2-related disorder

Similar variants

DCHS2 c.2477-1G>T Uncertain significance ★ same condition
DCHS2 p.Ala952Thr Uncertain significance same condition
DCHS2 p.Ile802Val Uncertain significance ⚠ same condition
DCHS2 p.Ser1397Phe Uncertain significance ⚠ same condition
DCHS2 c.2053-13755G>A Likely benign same condition
DCHS2 c.2053-13815C>T Benign same condition
DCHS2 c.2244+3329T>C Benign same condition
DCHS2 c.2477-8381C>T Benign 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/dchs2-p-ser562 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown