Is DVL1 p.Asn508Ser (c.1523A>G) pathogenic?

DVL1 p.Asn508Ser (c.1523A>G) is classified Conflicting classifications of pathogenicity in DVL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-20). AlphaMissense: likely benign (0.0644); Ultra-rare (popmax 0.0174%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DVL1 p.Asn508Ser (c.1523A>G)?

DVL1 p.Asn508Ser (c.1523A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DVL1 p.Asn508Ser (c.1523A>G) in the general population?

DVL1 p.Asn508Ser (c.1523A>G) is ultra-rare (popmax 0.0174%, nfe) (gnomAD).

What do computational predictors say about DVL1 p.Asn508Ser (c.1523A>G)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

DVL1 p.Asn508Ser

c.1523A>G · rs368987984 · VCV1364784

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -7.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.35	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.058	GERP -3.9, phastCons 0.9
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	19.06	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 0.0174% European (non-Finnish) · 205/1,176,734 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.014% 225/1,606,942 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0174%	5,740
Remaining individualsnot grpmax-eligible	0.0161%	6,219
Ashkenazi Jewishnot grpmax-eligible	0.0103%	9,740
Admixed American	0.0101%	9,933
African / African-American	0.00134%	74,848

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.Asn508Ser
Coding: c.1523A>G
MANE Select: NM_001330311
dbSNP: rs368987984
Type: single nucleotide variant
Location: chr1:1338168 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
DVL1 p.Arg108Trp Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg149Gln Uncertain significance ★★ ⚠ same condition
DVL1 p.Arg150Cys 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-asn508ser (accessed [today's date]).

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