Is DCHS1 p.Val286Ala (c.857T>C) pathogenic?

DCHS1 p.Val286Ala (c.857T>C) is classified Conflicting classifications of pathogenicity in DCHS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0548); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCHS1 p.Val286Ala (c.857T>C)?

DCHS1 p.Val286Ala (c.857T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCHS1 p.Val286Ala (c.857T>C) in the general population?

DCHS1 p.Val286Ala (c.857T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DCHS1 p.Val286Ala (c.857T>C)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

DCHS1 p.Val286Ala

c.857T>C · VCV4616990

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.054	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	18.13	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Overall 0.000657% 1/152,172 alleles · very rare

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.Val286Ala
Coding: c.857T>C
MANE Select: NM_003737
Type: single nucleotide variant
Location: chr11:6640757 (GRCh38)
Gene constraint: LOEUF 0.491 · pLI 0.33 · ClinGen HI 1/3 (gnomAD)
Residue 286: the cadherin 3 domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCHS1 p.Val286= Likely benign ★ same residue
DCHS1 p.Ala1454Val Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1460Pro Uncertain significance ★★ same condition
DCHS1 p.Ala1490Glu Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1547Gly Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1564Gly Uncertain significance ★★ ⚠ same condition
DCHS1 p.Ala1673Val Uncertain significance ★★ same condition
DCHS1 p.Ala1754Ser 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-val286ala (accessed [today's date]).

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