Is DVL1 p.Cys688= (c.2064C>T) pathogenic?

DVL1 p.Cys688= (c.2064C>T) is classified Likely benign in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Ultra-rare (popmax 0.0103%, nfe).

How common is DVL1 p.Cys688= (c.2064C>T) in the general population?

DVL1 p.Cys688= (c.2064C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

DVL1 p.Cys688=

c.2064C>T · rs770370467 · VCV2079190

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, 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
Pangolin	Δ0.27	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -3	GERP -1.3
Overall
CADD	2.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 120/1,166,918 alleles

Filtering AF 0.00877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00821%

Overall 0.00819% 129/1,575,346 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,724
Remaining individualsnot grpmax-eligible	0.00651%	15,352
African / African-American	0.00537%	18,639
Admixed American	0.00176%	56,976

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.Cys688=
Coding: c.2064C>T
MANE Select: NM_001330311
dbSNP: rs770370467
Type: single nucleotide variant
Location: chr1:1336166 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB

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

Similar variants

DVL1 p.Cys688Arg Uncertain significance ★ ⚠ same residue
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

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-cys688 (accessed [today's date]).

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