Is DVL1 p.Ala84Ser (c.250G>T) pathogenic?

DVL1 p.Ala84Ser (c.250G>T) is classified Uncertain significance in DVL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely benign (0.0921); Very rare (popmax 0.00267%, afr); Associated with ciliary dyskinesia, primary, 40.

What condition is associated with DVL1 p.Ala84Ser (c.250G>T)?

DVL1 p.Ala84Ser (c.250G>T) is associated with ciliary dyskinesia, primary, 40 (ClinVar).

How common is DVL1 p.Ala84Ser (c.250G>T) in the general population?

DVL1 p.Ala84Ser (c.250G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DVL1 p.Ala84Ser (c.250G>T)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

DVL1 p.Ala84Ser

c.250G>T · VCV4280078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ciliary dyskinesia, primary, 40

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.211	benign-leaning
SaProt	LLR -5.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 13 kb · p 2.8e-06 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,890 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,216 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.Ala84Ser
Coding: c.250G>T
MANE Select: NM_001330311
Type: single nucleotide variant
Location: chr1:1342475 (GRCh38)
Gene constraint: LOEUF 1.046 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 3 PDB
Residue 84: the dix domain

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

Disease context

ciliary dyskinesia, primary, 40 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DVL1 p.Ala84Gly Benign ★ 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-ala84ser (accessed [today's date]).

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