Is LRRK2 p.Ser3= (c.9T>C) pathogenic?

LRRK2 p.Ser3= (c.9T>C) is classified Likely benign in LRRK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-19). Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with LRRK2 p.Ser3= (c.9T>C)?

LRRK2 p.Ser3= (c.9T>C) is associated with Inborn genetic diseases (ClinVar).

How common is LRRK2 p.Ser3= (c.9T>C) in the general population?

LRRK2 p.Ser3= (c.9T>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

LRRK2 p.Ser3=

c.9T>C · rs1940799699 · VCV1768951

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	GERP -1.6, phastCons 0.45
Overall
CADD	12.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,986 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,850 alleles · very rare exomes 2/1,461,602 · genomes 0/152,248 · joint denominator

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: LRRK2
Protein: p.Ser3=
Coding: c.9T>C
MANE Select: NM_198578
dbSNP: rs1940799699
Type: single nucleotide variant
Location: chr12:40225140 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 58 PDB
Residue 3: the 'required for rab29-mediated activation' region

Full LRRK2 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

LRRK2 p.Ala1396Ser Uncertain significance ★★ ⚠ same condition
LRRK2 p.Ala1413Glu Uncertain significance ★★ ⚠ same condition
LRRK2 p.Ala1430Val Uncertain significance ★★ ⚠ same condition
LRRK2 p.Ala1440Val Uncertain significance ★★ same condition
LRRK2 p.Ala1572Thr Uncertain significance ★★ ⚠ same condition
LRRK2 p.Ala1659Gly Uncertain significance ★★ same condition
LRRK2 p.Ala233Val Uncertain significance ★★ ⚠ same condition
LRRK2 p.Ala417Val 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/lrrk2-p-ser3 (accessed [today's date]).

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