Is DVL1 p.Arg150Cys (c.448C>T) pathogenic?

DVL1 p.Arg150Cys (c.448C>T) is classified Uncertain significance in DVL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely benign (0.1501); Ultra-rare (popmax 0.0107%, amr); Associated with Inborn genetic diseases.

What condition is associated with DVL1 p.Arg150Cys (c.448C>T)?

DVL1 p.Arg150Cys (c.448C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DVL1 p.Arg150Cys (c.448C>T) in the general population?

DVL1 p.Arg150Cys (c.448C>T) is ultra-rare (popmax 0.0107%, amr) (gnomAD).

What do computational predictors say about DVL1 p.Arg150Cys (c.448C>T)?

AlphaMissense predicts likely benign (score 0.1501) — an in-silico prediction, not a clinical call.

DVL1 p.Arg150Cys

c.448C>T · rs769077276 · VCV2732352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1501 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1501	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -12.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.081, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	34.0	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 0.0107% Admixed American · 6/55,858 alleles

Filtering AF 0.00467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00428%

Overall 0.00511% 81/1,583,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0107%	9,310
European (non-Finnish)	0.00583%	17,141
Remaining individualsnot grpmax-eligible	0.0049%	20,418
South Asian	0.00344%	29,055
African / African-American	0.00134%	74,460

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.Arg150Cys
Coding: c.448C>T
MANE Select: NM_001330311
dbSNP: rs769077276
Type: single nucleotide variant
Location: chr1:1342071 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 150: the 'disordered' region

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.Arg164Gly 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-arg150cys (accessed [today's date]).

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