Is DCHS2 p.Asp1349= (c.4047C>T) pathogenic?

DCHS2 p.Asp1349= (c.4047C>T) is classified Benign in DCHS2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-11). Low-frequency (popmax 1.06%, afr); Associated with DCHS2-related disorder.

What condition is associated with DCHS2 p.Asp1349= (c.4047C>T)?

DCHS2 p.Asp1349= (c.4047C>T) is associated with DCHS2-related disorder (ClinVar).

How common is DCHS2 p.Asp1349= (c.4047C>T) in the general population?

DCHS2 p.Asp1349= (c.4047C>T) is low-frequency (popmax 1.06%, afr) (gnomAD).

DCHS2 p.Asp1349=

c.4047C>T · rs142864637 · VCV3034489

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, afr)

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 1.6	GERP -5.4, phastCons 1
Overall
CADD	10.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.06% African / African-American · 797/75,020 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.977%

Overall 0.0636% 1,026/1,613,190 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.06%	94
Remaining individualsnot grpmax-eligible	0.0929%	1,077
Admixed American	0.0802%	1,247
Middle Eastern	0.0496%	2,015
South Asian	0.0176%	5,688
European (non-Finnish)	0.00856%	11,679
East Asian	0.00669%	14,941

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.Asp1349=
Coding: c.4047C>T
MANE Select: NM_001358235
dbSNP: rs142864637
Type: single nucleotide variant
Location: chr4:154322460 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Residue 1349: the cadherin 12 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-asp1349 (accessed [today's date]).

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