Is DVL1 p.Arg151Trp (c.451C>T) pathogenic?

DVL1 p.Arg151Trp (c.451C>T) is classified Likely benign in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.1858); Rare (popmax 0.233%, sas).

How common is DVL1 p.Arg151Trp (c.451C>T) in the general population?

DVL1 p.Arg151Trp (c.451C>T) is rare (popmax 0.233%, sas) (gnomAD).

What do computational predictors say about DVL1 p.Arg151Trp (c.451C>T)?

AlphaMissense predicts likely benign (score 0.1858) — an in-silico prediction, not a clinical call.

DVL1 p.Arg151Trp

c.451C>T · rs540790160 · VCV1488127

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1858 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1858	likely benign
REVEL	0.107	moderately benign-leaning
SaProt	LLR -12.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.4	GERP -1.4, phastCons 1
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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.233% South Asian · 203/87,074 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.0147% 232/1,583,298 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.233%	429
Remaining individualsnot grpmax-eligible	0.0131%	7,654
Admixed American	0.00896%	11,160
East Asian	0.0023%	43,438
African / African-American	0.00134%	74,566
European (non-Finnish)	0.0012%	83,224

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.Arg151Trp
Coding: c.451C>T
MANE Select: NM_001330311
dbSNP: rs540790160
Type: single nucleotide variant
Location: chr1:1342068 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 151: the 'disordered' region

Full DVL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DVL1 p.Arg151Gln Uncertain significance ★ ⚠ same residue
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

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-arg151trp (accessed [today's date]).

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