Is DVL3 p.Ser241Phe (c.722C>T) pathogenic?

DVL3 p.Ser241Phe (c.722C>T) is classified Uncertain significance in DVL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-31). AlphaMissense: likely pathogenic (0.9907); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with DVL3 p.Ser241Phe (c.722C>T)?

DVL3 p.Ser241Phe (c.722C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DVL3 p.Ser241Phe (c.722C>T) in the general population?

DVL3 p.Ser241Phe (c.722C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DVL3 p.Ser241Phe (c.722C>T)?

AlphaMissense predicts likely pathogenic (score 0.9907) — an in-silico prediction, not a clinical call.

DVL3 p.Ser241Phe

c.722C>T · rs758184432 · VCV2875098

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9907	likely pathogenic
REVEL	0.291	indeterminate
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.58, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 4e-06 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/75,004 alleles

Overall 0.000137% 2/1,461,862 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,004
European (non-Finnish)	8.47e-05%	1,180,004

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: DVL3
Protein: p.Ser241Phe
Coding: c.722C>T
MANE Select: NM_004423
dbSNP: rs758184432
Type: single nucleotide variant
Location: chr3:184165450 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 59.50 · 9 PDB

Full DVL3 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

DVL3 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala565Val Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala593Val Uncertain significance ★★ ⚠ same condition
DVL3 p.Ala629Thr Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg145Gln Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg157Gln Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg166Trp Uncertain significance ★★ ⚠ same condition
DVL3 p.Arg167Gln 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/dvl3-p-ser241phe (accessed [today's date]).

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