Is DVL1 p.Ala352Pro (c.1054G>C) pathogenic?

DVL1 p.Ala352Pro (c.1054G>C) is classified Uncertain significance in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-13). AlphaMissense: likely benign (0.1544); Very rare (popmax 0.00034%, nfe).

How common is DVL1 p.Ala352Pro (c.1054G>C) in the general population?

DVL1 p.Ala352Pro (c.1054G>C) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about DVL1 p.Ala352Pro (c.1054G>C)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

DVL1 p.Ala352Pro

c.1054G>C · rs1036119113 · VCV2172481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.009	GERP -5.3, phastCons 0.76
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	32.0	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 0.00034% European (non-Finnish) · 4/1,176,132 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000275% 4/1,453,702 alleles · very 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: DVL1
Protein: p.Ala352Pro
Coding: c.1054G>C
MANE Select: NM_001330311
dbSNP: rs1036119113
Type: single nucleotide variant
Location: chr1:1339582 (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.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-ala352pro (accessed [today's date]).

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