Is LPAR2 p.Pro140Leu (c.419C>T) pathogenic?

LPAR2 p.Pro140Leu (c.419C>T) is classified Uncertain significance in LPAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.396); Very rare (popmax 0.000171%, nfe).

How common is LPAR2 p.Pro140Leu (c.419C>T) in the general population?

LPAR2 p.Pro140Leu (c.419C>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about LPAR2 p.Pro140Leu (c.419C>T)?

AlphaMissense predicts ambiguous (score 0.396) — an in-silico prediction, not a clinical call.

LPAR2 p.Pro140Leu

c.419C>T · VCV3539114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.396 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Computational evidence

Protein change
AlphaMissense	0.396	ambiguous
REVEL	0.078	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 3,025 bp · p 0.0011 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P143L vs ClinVar P140L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,170,990 alleles

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

Overall 0.000139% 2/1,441,612 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: LPAR2
Protein: p.Pro140Leu
Coding: c.419C>T
MANE Select: NM_001395660
Type: single nucleotide variant
Location: chr19:19626857 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.62 · 2 PDB

Full LPAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LPAR2 c.531C>T Benign ★★ same type
LPAR2 c.-1C>G Uncertain significance ★ ⚠ same type
LPAR2 p.Ala171Val Uncertain significance ★ ⚠ same type
LPAR2 p.Ala188Val Uncertain significance ★ ⚠ same type
LPAR2 p.Ala310Thr Uncertain significance ★ ⚠ same type
LPAR2 p.Ala55Pro Uncertain significance ★ ⚠ same type
LPAR2 p.Ala55Val Uncertain significance ★ ⚠ same type
LPAR2 p.Ala94Ser 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/lpar2-p-pro140leu (accessed [today's date]).

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