Is LRRK2 p.Pro2103= (c.6309A>G) pathogenic?

LRRK2 p.Pro2103= (c.6309A>G) is classified Likely benign in LRRK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-01). Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRRK2 p.Pro2103= (c.6309A>G)?

LRRK2 p.Pro2103= (c.6309A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LRRK2 p.Pro2103= (c.6309A>G) in the general population?

LRRK2 p.Pro2103= (c.6309A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

LRRK2 p.Pro2103=

c.6309A>G · rs2499972545 · VCV1752762

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -0.57	GERP -2.7
Overall
CADD	5.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,038 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,612,416 alleles · very rare exomes 4/1,460,086 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,519
European (non-Finnish)	0.00017%	589,338

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.Pro2103=
Coding: c.6309A>G
MANE Select: NM_198578
dbSNP: rs2499972545
Type: single nucleotide variant
Location: chr12:40348437 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 58 PDB
Residue 2103: the protein kinase domain; an α-helix; a binding site

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.Pro2103Ser Uncertain significance ★ ⚠ same residue
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

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-pro2103 (accessed [today's date]).

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