Is DVL1 p.Glu672Ala (c.2015A>C) pathogenic?

DVL1 p.Glu672Ala (c.2015A>C) is classified Uncertain significance in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.4418); Very rare (popmax 0.00405%, afr); Associated with Inborn genetic diseases.

What condition is associated with DVL1 p.Glu672Ala (c.2015A>C)?

DVL1 p.Glu672Ala (c.2015A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DVL1 p.Glu672Ala (c.2015A>C) in the general population?

DVL1 p.Glu672Ala (c.2015A>C) is very rare (popmax 0.00405%, afr) (gnomAD).

What do computational predictors say about DVL1 p.Glu672Ala (c.2015A>C)?

AlphaMissense predicts ambiguous (score 0.4418) — an in-silico prediction, not a clinical call.

DVL1 p.Glu672Ala

c.2015A>C · rs940589568 · VCV2280236

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00405%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4418	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -5.49	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	23.9	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 0.00405% African / African-American · 3/74,098 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000498%

Overall 0.000256% 4/1,559,668 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00405%	24,699
East Asian	0.00235%	42,618

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.Glu672Ala
Coding: c.2015A>C
MANE Select: NM_001330311
dbSNP: rs940589568
Type: single nucleotide variant
Location: chr1:1336215 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DVL1 p.Ala125Val Uncertain significance ★★ ⚠ same condition
DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same condition
DVL1 p.Ala361Thr Uncertain significance ★★ ⚠ same condition
DVL1 p.Ala368Val Uncertain significance ★★ ⚠ same condition
DVL1 p.Ala667Pro Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg108Trp Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg149Gln Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg150Cys 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/dvl1-p-glu672ala (accessed [today's date]).

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