Is LRRK2 p.Ala172= (c.516C>T) pathogenic?

LRRK2 p.Ala172= (c.516C>T) is classified Likely benign in LRRK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRRK2 p.Ala172= (c.516C>T)?

LRRK2 p.Ala172= (c.516C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRRK2 p.Ala172= (c.516C>T) in the general population?

LRRK2 p.Ala172= (c.516C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

LRRK2 p.Ala172=

c.516C>T · rs1941550609 · VCV2608575

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, 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 0.79, phastCons 0.18
Overall
CADD	12.55	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,870 alleles

Overall 6.2e-05% 1/1,613,470 alleles · very rare exomes 0/1,461,378 · genomes 1/152,092 · 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.Ala172=
Coding: c.516C>T
MANE Select: NM_198578
dbSNP: rs1941550609
Type: single nucleotide variant
Location: chr12:40238048 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 77.64 · 58 PDB
Residue 172: 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.Ala172Val 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-ala172 (accessed [today's date]).

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