Is DVL1 p.Ser490= (c.1470C>G) pathogenic?

DVL1 p.Ser490= (c.1470C>G) is classified Benign/Likely benign in DVL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Ultra-rare (popmax 0.0412%, nfe).

How common is DVL1 p.Ser490= (c.1470C>G) in the general population?

DVL1 p.Ser490= (c.1470C>G) is ultra-rare (popmax 0.0412%, nfe) (gnomAD).

DVL1 p.Ser490=

c.1470C>G · rs149343423 · VCV1586315

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0412%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9	GERP -4.6
Overall
CADD	0.123	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0412% European (non-Finnish) · 486/1,178,758 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0369%

Overall 0.0376% 605/1,608,252 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.125%	797
Remaining individualsnot grpmax-eligible	0.0481%	2,080
European (non-Finnish)grpmax	0.0412%	2,425
Finnishnot grpmax-eligible	0.0257%	3,896
South Asian	0.022%	4,542
Middle Eastern	0.0165%	6,058
Admixed American	0.0152%	6,596
African / African-American	0.00815%	12,263

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DVL1
Protein: p.Ser490=
Coding: c.1470C>G
MANE Select: NM_001330311
dbSNP: rs149343423
Type: single nucleotide variant
Location: chr1:1338306 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 490: the dep domain

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

Similar variants

DVL1 p.Ala125Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala361Thr Uncertain significance ★★ ⚠ same type
DVL1 p.Ala368Val Uncertain significance ★★ ⚠ same type
DVL1 p.Ala667Pro Uncertain significance ★★ ⚠ same type
DVL1 p.Arg108Trp Uncertain significance ★★ ⚠ same type
DVL1 p.Arg116Gln Uncertain significance ★★ ⚠ same type
DVL1 p.Arg128Cys Uncertain significance ★★ ⚠ 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/dvl1-p-ser490 (accessed [today's date]).

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