Is DVL3 p.Arg342Cys (c.1024C>T) pathogenic?

DVL3 p.Arg342Cys (c.1024C>T) is classified Uncertain significance in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.1797); Ultra-rare (popmax 0.0356%, eas); Associated with Inborn genetic diseases.

What condition is associated with DVL3 p.Arg342Cys (c.1024C>T)?

DVL3 p.Arg342Cys (c.1024C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DVL3 p.Arg342Cys (c.1024C>T) in the general population?

DVL3 p.Arg342Cys (c.1024C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about DVL3 p.Arg342Cys (c.1024C>T)?

AlphaMissense predicts likely benign (score 0.1797) — an in-silico prediction, not a clinical call.

DVL3 p.Arg342Cys

c.1024C>T · rs560181896 · VCV3086401

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1797	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -12.86	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 4e-06 · regional, not allelic
Overall
CADD	32.0	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 0.0356% East Asian · 16/44,886 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00142% 23/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
Remaining individualsnot grpmax-eligible	0.0032%	31,251
South Asian	0.0022%	45,542
European (non-Finnish)	0.000254%	393,340

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.Arg342Cys
Coding: c.1024C>T
MANE Select: NM_004423
dbSNP: rs560181896
Type: single nucleotide variant
Location: chr3:184166649 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 342: a modified residue (omega-n-methylarginine; alternate); a modified residue (symmetric dimethylarginine; by prmt7; alternate)

Full DVL3 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

DVL3 p.Arg342His Uncertain significance ★★ ⚠ same residue
DVL3 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala565Val Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala593Val Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala629Thr Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg145Gln Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg157Gln Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg166Trp 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/dvl3-p-arg342cys (accessed [today's date]).

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