Is DVL1 p.Pro658= (c.1974C>T) pathogenic?

DVL1 p.Pro658= (c.1974C>T) is classified Benign in DVL1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 6.54%, afr) — too common for a highly-penetrant pathogenic allele.

DVL1 p.Pro658=

Q: How common is DVL1 p.Pro658= (c.1974C>T) in the general population?

DVL1 p.Pro658= (c.1974C>T) is common (popmax 6.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1974C>T · rs34935417 · VCV1168660

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.54%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.1
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.54% African / African-American · 4,859/74,266 alleles

Filtering AF 6.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.33%

Overall 0.366% 5,701/1,559,656 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.54%	15
Admixed American	0.496%	202
Remaining individualsnot grpmax-eligible	0.48%	208
Middle Eastern	0.416%	240
European (non-Finnish)	0.0215%	4,654
South Asian	0.0116%	8,639
East Asian	0.00235%	42,562

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.Pro658=
Coding: c.1974C>T
MANE Select: NM_001330311
dbSNP: rs34935417
Type: single nucleotide variant
Location: chr1:1336256 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 658: the 'disordered' region

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

Similar variants

DVL1 p.Pro658Leu 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-pro658 (accessed [today's date]).

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