Is DVL1 p.Ser628Ile (c.1883G>T) pathogenic?

DVL1 p.Ser628Ile (c.1883G>T) is classified Uncertain significance in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-22). AlphaMissense: likely benign (0.1269); Very rare (popmax 8.5e-05%, nfe).

How common is DVL1 p.Ser628Ile (c.1883G>T) in the general population?

DVL1 p.Ser628Ile (c.1883G>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about DVL1 p.Ser628Ile (c.1883G>T)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

DVL1 p.Ser628Ile

c.1883G>T · rs749795230 · VCV1309231

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -10.11	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 7.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	23.0	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 8.5e-05% European (non-Finnish) · 1/1,176,500 alleles

Overall 6.94e-05% 1/1,440,884 alleles · very rare

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.Ser628Ile
Coding: c.1883G>T
MANE Select: NM_001330311
dbSNP: rs749795230
Type: single nucleotide variant
Location: chr1:1336347 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 628: the 'disordered' region

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

Similar variants

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
DVL1 p.Arg128Cys 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-ser628ile (accessed [today's date]).

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