Is DVL3 p.Asp136Ala (c.407A>C) pathogenic?

DVL3 p.Asp136Ala (c.407A>C) is classified Uncertain significance in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-14). AlphaMissense: likely benign (0.1935); Absent from gnomAD v4.1.

How common is DVL3 p.Asp136Ala (c.407A>C) in the general population?

DVL3 p.Asp136Ala (c.407A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DVL3 p.Asp136Ala (c.407A>C)?

AlphaMissense predicts likely benign (score 0.1935) — an in-silico prediction, not a clinical call.

DVL3 p.Asp136Ala

c.407A>C · rs2473697760 · VCV2814295

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1935	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -3.50	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 4e-06 · regional, not allelic
Overall
CADD	23.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DVL3
Protein: p.Asp136Ala
Coding: c.407A>C
MANE Select: NM_004423
dbSNP: rs2473697760
Type: single nucleotide variant
Location: chr3:184164545 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 136: 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-asp136ala (accessed [today's date]).

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