Is DVL3 p.Ser112= (c.336C>T) pathogenic?

DVL3 p.Ser112= (c.336C>T) is classified Likely benign in DVL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). Ultra-rare (popmax 0.0173%, afr).

How common is DVL3 p.Ser112= (c.336C>T) in the general population?

DVL3 p.Ser112= (c.336C>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

DVL3 p.Ser112=

c.336C>T · VCV3614224

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

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
Constraint at this position
Conservation	phyloP -0.18	GERP -3, phastCons 0.3
Overall
CADD	6.948	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/75,036 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.000805% 13/1,613,982 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.Ser112=
Coding: c.336C>T
MANE Select: NM_004423
Type: single nucleotide variant
Location: chr3:184164371 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB
Residue 112: the 'disordered' region

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

Similar variants

DVL3 p.Ser112Phe Uncertain significance ★ ⚠ same residue
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

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-ser112 (accessed [today's date]).

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