Is DVL1 p.Arg233Pro (c.698G>C) pathogenic?

DVL1 p.Arg233Pro (c.698G>C) is classified Conflicting classifications of pathogenicity in DVL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-11). AlphaMissense: ambiguous (0.4196); Very rare (popmax 0.00467%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DVL1 p.Arg233Pro (c.698G>C)?

DVL1 p.Arg233Pro (c.698G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DVL1 p.Arg233Pro (c.698G>C) in the general population?

DVL1 p.Arg233Pro (c.698G>C) is very rare (popmax 0.00467%, nfe) (gnomAD).

What do computational predictors say about DVL1 p.Arg233Pro (c.698G>C)?

AlphaMissense predicts ambiguous (score 0.4196) — an in-silico prediction, not a clinical call.

DVL1 p.Arg233Pro

c.698G>C · rs776763302 · VCV1935671

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00467%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4196	ambiguous
REVEL	0.233	benign-leaning
SaProt	LLR -13.47	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 2.5, phastCons 0.84
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	26.6	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 0.00467% European (non-Finnish) · 55/1,178,632 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.0046% 74/1,609,534 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0508%	1,967
European (non-Finnish)grpmax	0.00467%	21,430
East Asian	0.00448%	22,333
Remaining individualsnot grpmax-eligible	0.00322%	31,104

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg233Pro
Coding: c.698G>C
MANE Select: NM_001330311
dbSNP: rs776763302
Type: single nucleotide variant
Location: chr1:1340411 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 233: 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.Arg233Leu Uncertain significance ★ ⚠ same residue
DVL1 p.Arg233Trp Uncertain significance ★ ⚠ same residue
DVL1 p.Arg233= Uncertain significance ★ same residue
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

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-arg233pro (accessed [today's date]).

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