Is DVL3 p.Ser622Arg (c.1866C>G) pathogenic?

DVL3 p.Ser622Arg (c.1866C>G) is classified Uncertain significance in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.6689); Ultra-rare (popmax 0.0166%, mid); Associated with Inborn genetic diseases.

What condition is associated with DVL3 p.Ser622Arg (c.1866C>G)?

DVL3 p.Ser622Arg (c.1866C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DVL3 p.Ser622Arg (c.1866C>G) in the general population?

DVL3 p.Ser622Arg (c.1866C>G) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DVL3 p.Ser622Arg (c.1866C>G)?

AlphaMissense predicts likely pathogenic (score 0.6689) — an in-silico prediction, not a clinical call.

DVL3 p.Ser622Arg

c.1866C>G · VCV4245687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6689 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6689	likely pathogenic
REVEL	0.081	moderately benign-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -3.1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,688 bp · p 0.69 · regional, not allelic
Overall
CADD	12.87	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 0.0166% Middle Eastern · 1/6,020 alleles

Overall 0.000126% 2/1,587,274 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,020
Admixed American	0.00183%	54,750

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.Ser622Arg
Coding: c.1866C>G
MANE Select: NM_004423
Type: single nucleotide variant
Location: chr3:184170470 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 622: the 'disordered' region

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.Ser622= Likely benign ★ 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-ser622arg (accessed [today's date]).

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