Is DVL3 p.Ser581fs (c.1743del) pathogenic?

DVL3 p.Ser581fs (c.1743del) is classified Uncertain significance in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Absent from gnomAD.

How common is DVL3 p.Ser581fs (c.1743del) in the general population?

DVL3 p.Ser581fs (c.1743del) is absent from gnomAD (gnomAD).

DVL3 p.Ser581fs

c.1743del · rs2473705754 · VCV2028424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DVL3
Protein: p.Ser581fs
Coding: c.1743del
MANE Select: NM_004423
dbSNP: rs2473705754
Type: Deletion
Location: chr3:184170347 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 581: the 'disordered' region

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

Similar variants

DVL3 p.Ser581= Likely benign ★ same residue
DVL3 p.Ala529fs Pathogenic ★ same type
DVL3 p.Asp584fs Pathogenic ★ same type
DVL3 p.Gln539fs Likely pathogenic ★ same type
DVL3 p.Gly582fs Likely pathogenic ★ same type
DVL3 p.Pro531fs Pathogenic ★ same type
DVL3 p.Ser573fs Pathogenic ★ same type
DVL3 p.Ser578fs 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-ser581fs (accessed [today's date]).

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