Is DCHS1 p.Trp1402Arg (c.4204T>C) pathogenic?

DCHS1 p.Trp1402Arg (c.4204T>C) is classified Uncertain significance in DCHS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-11). AlphaMissense: likely benign (0.1883); Very rare (popmax 0.000174%, nfe); Associated with van Maldergem syndrome 1.

What condition is associated with DCHS1 p.Trp1402Arg (c.4204T>C)?

DCHS1 p.Trp1402Arg (c.4204T>C) is associated with van Maldergem syndrome 1 (ClinVar).

How common is DCHS1 p.Trp1402Arg (c.4204T>C) in the general population?

DCHS1 p.Trp1402Arg (c.4204T>C) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about DCHS1 p.Trp1402Arg (c.4204T>C)?

AlphaMissense predicts likely benign (score 0.1883) — an in-silico prediction, not a clinical call.

DCHS1 p.Trp1402Arg

c.4204T>C · rs2493825272 · VCV3254745

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

van Maldergem syndrome 1

Computational evidence

Protein change
AlphaMissense	0.1883	likely benign
REVEL	0.317	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 0.69, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,149,756 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00013% 2/1,539,084 alleles · very rare exomes 2/1,386,886 · genomes 0/152,198 · joint denominator

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.Trp1402Arg
Coding: c.4204T>C
MANE Select: NM_003737
dbSNP: rs2493825272
Type: single nucleotide variant
Location: chr11:6630590 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 1402: the cadherin 13 domain

Full DCHS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

van Maldergem syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCHS1 p.Ala1325Ser Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala2550Glu Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala2815Thr Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala2817Pro Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala486Val Uncertain significance ★★ ⚠ same condition
DCHS1 p.Arg1229Cys Uncertain significance ★★ ⚠ same condition
DCHS1 p.Arg1229Leu Uncertain significance ★★ ⚠ same condition
DCHS1 p.Arg132Gln Uncertain significance ★★ ⚠ 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/dchs1-p-trp1402arg (accessed [today's date]).

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