Is DVL3 p.Arg619= (c.1857G>T) pathogenic?

DVL3 p.Arg619= (c.1857G>T) is classified Likely benign in DVL3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-06). Rare (popmax 0.142%, sas); Associated with DVL3-related disorder.

What condition is associated with DVL3 p.Arg619= (c.1857G>T)?

DVL3 p.Arg619= (c.1857G>T) is associated with DVL3-related disorder (ClinVar).

How common is DVL3 p.Arg619= (c.1857G>T) in the general population?

DVL3 p.Arg619= (c.1857G>T) is rare (popmax 0.142%, sas) (gnomAD).

DVL3 p.Arg619=

c.1857G>T · rs569284285 · VCV3038425

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.142%, sas)

Conditions

DVL3-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 0.52	GERP -3.1, phastCons 0.99
Overall
CADD	6.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% South Asian · 125/87,964 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00802% 127/1,584,188 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.142%	704
Remaining individualsnot grpmax-eligible	0.00327%	30,618

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: DVL3
Protein: p.Arg619=
Coding: c.1857G>T
MANE Select: NM_004423
dbSNP: rs569284285
Type: single nucleotide variant
Location: chr3:184170461 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 619: the 'disordered' region

Full DVL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DVL3-related disorder

Similar variants

DVL3 p.Ser646Arg Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg73Gln Uncertain significance ★ ⚠ same condition
DVL3 p.Asp510Tyr Uncertain significance ★ ⚠ same condition
DVL3 p.Pro683Leu Uncertain significance ★ ⚠ same condition
DVL3 c.354-6C>T Likely benign same condition
DVL3 c.763+9G>A Likely benign same condition
DVL3 p.Arg113= Likely benign same condition
DVL3 c.1715-1G>A Pathogenic/Likely pathogenic ★★ 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/dvl3-p-arg619 (accessed [today's date]).

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