Is DVL1 p.Ser567fs (c.1695del) pathogenic?

DVL1 p.Ser567fs (c.1695del) is classified Pathogenic in DVL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-18). Associated with autosomal dominant Robinow syndrome 2.

What condition is associated with DVL1 p.Ser567fs (c.1695del)?

DVL1 p.Ser567fs (c.1695del) is associated with autosomal dominant Robinow syndrome 2 (ClinVar).

DVL1 p.Ser567fs

c.1695del · VCV3764194

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal dominant Robinow syndrome 2

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, 19 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 0.83	GERP -4, phastCons 0.21

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

Variant & gene context

Gene: DVL1
Protein: p.Ser567fs
Coding: c.1695del
MANE Select: NM_001330311
Type: Deletion
Location: chr1:1337996 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 567: the 'disordered' region

Full DVL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant Robinow syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DVL1 p.Pro524fs Pathogenic/Likely pathogenic ★★ same condition
DVL1 p.Thr516fs Pathogenic/Likely pathogenic ★★ same condition
DVL1 p.Trp532fs Pathogenic ★★ same condition
DVL1 p.Gly535fs Pathogenic ★ same condition
DVL1 p.Gly544fs Pathogenic ★ same condition
DVL1 p.His527fs Pathogenic ★ same condition
DVL1 p.Pro528fs Pathogenic ★ same condition
DVL1 p.Pro533fs 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/dvl1-p-ser567fs (accessed [today's date]).

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