Is LPP p.Pro363Ser (c.1087C>T) pathogenic?

LPP p.Pro363Ser (c.1087C>T) is classified Benign in LPP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-14). AlphaMissense: likely benign (0.0618); Rare (popmax 0.54%, afr); Associated with LPP-related disorder.

What condition is associated with LPP p.Pro363Ser (c.1087C>T)?

LPP p.Pro363Ser (c.1087C>T) is associated with LPP-related disorder (ClinVar).

How common is LPP p.Pro363Ser (c.1087C>T) in the general population?

LPP p.Pro363Ser (c.1087C>T) is rare (popmax 0.54%, afr) (gnomAD).

What do computational predictors say about LPP p.Pro363Ser (c.1087C>T)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

LPP p.Pro363Ser

c.1087C>T · rs146042962 · VCV3046026

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.54%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

LPP-related disorder

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.50	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 1.8	GERP 1.1, phastCons 0.8
Regional constraint	o/e 1.15	unconstrained · MANE · 468 kb · p 2.3e-05 · regional, not allelic
Overall
CADD	17.64	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.54% African / African-American · 405/74,974 alleles

Filtering AF 0.497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.48%

Overall 0.0317% 511/1,612,548 alleles · rare exomes 273/1,460,304 · genomes 238/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.54%	185
Remaining individualsnot grpmax-eligible	0.0432%	2,313
Middle Eastern	0.0331%	3,021
Admixed American	0.0167%	5,992
South Asian	0.0077%	12,995
European (non-Finnish)	0.00492%	20,335
East Asian	0.00446%	22,433

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: LPP
Protein: p.Pro363Ser
Coding: c.1087C>T
MANE Select: NM_001375462
dbSNP: rs146042962
Type: single nucleotide variant
Location: chr3:188609818 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 363: the 'disordered' region

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

Disease context

LPP-related disorder

Similar variants

LPP c.1589+8A>G Likely benign same condition
LPP p.Ala302= Likely benign same condition
LPP p.Arg22Trp Likely benign ⚠ same condition
LPP p.Gly245= Likely benign same condition
LPP p.Ser145= Likely benign same condition
LPP p.Thr212Met Likely benign ⚠ same condition
LPP p.Arg140Trp Uncertain significance ★★ ⚠ same type
LPP c.1113+51T>C Benign ★★ 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/lpp-p-pro363ser (accessed [today's date]).

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