Is DVL3 p.Ser564fs (c.1688dup) pathogenic?

DVL3 p.Ser564fs (c.1688dup) is classified Likely pathogenic in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-15). Associated with autosomal dominant Robinow syndrome 3.

What condition is associated with DVL3 p.Ser564fs (c.1688dup)?

DVL3 p.Ser564fs (c.1688dup) is associated with autosomal dominant Robinow syndrome 3 (ClinVar).

DVL3 p.Ser564fs

c.1688dup · VCV3775469

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal dominant Robinow syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (14 of 15, 31 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -3.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DVL3
Protein: p.Ser564fs
Coding: c.1688dup
MANE Select: NM_004423
Type: Duplication
Location: chr3:184170190 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 564: the 'disordered' region

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

Disease context

autosomal dominant Robinow syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DVL3 c.1715-1G>A Pathogenic/Likely pathogenic ★★ same condition
DVL3 p.Arg317Gln Uncertain significance ★★ ⚠ same condition
DVL3 p.Glu270Lys Uncertain significance ★★ ⚠ same condition
DVL3 c.1715-2A>G Pathogenic ★ same condition
DVL3 p.Ala529fs Pathogenic ★ same condition
DVL3 p.Asp584fs Pathogenic ★ same condition
DVL3 p.Pro531fs Pathogenic ★ same condition
DVL3 p.Ser573fs Pathogenic ★ 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/dvl3-p-ser564fs (accessed [today's date]).

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