Is DVL3 p.Pro672Leu (c.2015C>T) pathogenic?

DVL3 p.Pro672Leu (c.2015C>T) is classified Uncertain significance in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely benign (0.0808); Ultra-rare (popmax 0.0269%, eas).

How common is DVL3 p.Pro672Leu (c.2015C>T) in the general population?

DVL3 p.Pro672Leu (c.2015C>T) is ultra-rare (popmax 0.0269%, eas) (gnomAD).

What do computational predictors say about DVL3 p.Pro672Leu (c.2015C>T)?

AlphaMissense predicts likely benign (score 0.0808) — an in-silico prediction, not a clinical call.

DVL3 p.Pro672Leu

c.2015C>T · rs753752963 · VCV1975259

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0808	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,688 bp · p 0.69 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0269% East Asian · 12/44,666 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000824% 12/1,456,658 alleles · ultra-rare

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.Pro672Leu
Coding: c.2015C>T
MANE Select: NM_004423
dbSNP: rs753752963
Type: single nucleotide variant
Location: chr3:184170619 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 672: the 'disordered' region

Full DVL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DVL3 c.1715-1G>A Pathogenic/Likely pathogenic ★★ same type
DVL3 p.Ala359Thr Uncertain significance ★★ ⚠ same type
DVL3 p.Ala565Val Uncertain significance ★★ ⚠ same type
DVL3 p.Ala593Val Uncertain significance ★★ ⚠ same type
DVL3 p.Ala629Thr Uncertain significance ★★ ⚠ same type
DVL3 p.Arg145Gln Uncertain significance ★★ ⚠ same type
DVL3 p.Arg157Gln Uncertain significance ★★ ⚠ same type
DVL3 p.Arg166Trp 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/dvl3-p-pro672leu (accessed [today's date]).

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