Is DYRK3 p.Pro44Ala (c.130C>G) pathogenic?

DYRK3 p.Pro44Ala (c.130C>G) is classified Uncertain significance in DYRK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-28). AlphaMissense: likely benign (0.0619); Ultra-rare (popmax 0.0111%, eas).

How common is DYRK3 p.Pro44Ala (c.130C>G) in the general population?

DYRK3 p.Pro44Ala (c.130C>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about DYRK3 p.Pro44Ala (c.130C>G)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

DYRK3 p.Pro44Ala

c.130C>G · VCV3274228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.53	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 3.3	GERP 0.54, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	18.29	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 0.0111% East Asian · 5/44,850 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00031% 5/1,613,748 alleles · ultra-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: DYRK3
Protein: p.Pro44Ala
Coding: c.130C>G
MANE Select: NM_003582
Type: single nucleotide variant
Location: chr1:206637702 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.21 · 1 PDB
Residue 44: the 'disordered' region

Full DYRK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DYRK3 p.Pro44Leu Uncertain significance ★ ⚠ same residue
DYRK3 p.Ala316Ser Uncertain significance ★ ⚠ same type
DYRK3 p.Ala509Ser Uncertain significance ★ ⚠ same type
DYRK3 p.Ala514Gly Uncertain significance ★ ⚠ same type
DYRK3 p.Arg241His Uncertain significance ★ ⚠ same type
DYRK3 p.Arg245His Uncertain significance ★ ⚠ same type
DYRK3 p.Arg248Cys Uncertain significance ★ ⚠ same type
DYRK3 p.Arg255Gln 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/dyrk3-p-pro44ala (accessed [today's date]).

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