Is DVL1 p.Arg388Pro (c.1163G>C) pathogenic?

DVL1 p.Arg388Pro (c.1163G>C) is classified Likely benign in DVL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-01). AlphaMissense: likely benign (0.1484); Ultra-rare (popmax 0.0528%, nfe); Associated with autosomal dominant Robinow syndrome 2.

What condition is associated with DVL1 p.Arg388Pro (c.1163G>C)?

DVL1 p.Arg388Pro (c.1163G>C) is associated with autosomal dominant Robinow syndrome 2 (ClinVar).

How common is DVL1 p.Arg388Pro (c.1163G>C) in the general population?

DVL1 p.Arg388Pro (c.1163G>C) is ultra-rare (popmax 0.0528%, nfe) (gnomAD).

What do computational predictors say about DVL1 p.Arg388Pro (c.1163G>C)?

AlphaMissense predicts likely benign (score 0.1484) — an in-silico prediction, not a clinical call.

DVL1 p.Arg388Pro

c.1163G>C · VCV3777766

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1484 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0528%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant Robinow syndrome 2

Computational evidence

Protein change
AlphaMissense	0.1484	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -5.00	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 -0.11	GERP -5.5, phastCons 0.037
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	21.6	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 0.0528% European (non-Finnish) · 606/1,146,900 alleles

Filtering AF 0.0493% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.048%

Overall 0.0431% 667/1,548,500 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0968%	1,033
European (non-Finnish)grpmax	0.0528%	1,893
African / African-American	0.00274%	36,495
Admixed American	0.00196%	50,980

Remaining individuals 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.Arg388Pro
Coding: c.1163G>C
MANE Select: NM_001330311
Type: single nucleotide variant
Location: chr1:1339331 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB

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

Disease context

autosomal dominant Robinow syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DVL1 p.Arg388His Likely benign ★ same residue
DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg116Gln Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg128Cys Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg40Gly Uncertain significance ★★ ⚠ same condition
DVL1 p.Glu85Asp Uncertain significance ★★ ⚠ same condition
DVL1 p.Ser246Phe Uncertain significance ★★ ⚠ same condition
DVL1 p.Thr253Met 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-arg388pro (accessed [today's date]).

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