Is DVL1 p.Arg580Trp (c.1738C>T) pathogenic?

DVL1 p.Arg580Trp (c.1738C>T) is classified Uncertain significance in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-09). AlphaMissense: likely benign (0.1585); Ultra-rare (popmax 0.0111%, afr).

How common is DVL1 p.Arg580Trp (c.1738C>T) in the general population?

DVL1 p.Arg580Trp (c.1738C>T) is ultra-rare (popmax 0.0111%, afr) (gnomAD).

What do computational predictors say about DVL1 p.Arg580Trp (c.1738C>T)?

AlphaMissense predicts likely benign (score 0.1585) — an in-silico prediction, not a clinical call.

DVL1 p.Arg580Trp

c.1738C>T · VCV3718167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1585 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1585	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -10.33	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 4.1	GERP 0.47, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	24.1	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 0.0111% African / African-American · 8/71,902 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00216% 33/1,529,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.012%	8,330
African / African-Americangrpmax	0.0111%	8,988
East Asian	0.0046%	21,742
Finnishnot grpmax-eligible	0.00213%	46,918
Remaining individualsnot grpmax-eligible	0.00169%	59,208
European (non-Finnish)	0.00148%	67,531
South Asian	0.00125%	80,014

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.Arg580Trp
Coding: c.1738C>T
MANE Select: NM_001330311
Type: single nucleotide variant
Location: chr1:1336492 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 580: the 'disordered' region

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

Similar variants

DVL1 p.Arg580Gln Conflicting classifications of pathogenicity ★ ⚠ 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-arg580trp (accessed [today's date]).

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