Is LYPLA1 p.Pro153Ser (c.457C>T) pathogenic?

LYPLA1 p.Pro153Ser (c.457C>T) is classified Benign in LYPLA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-24). AlphaMissense: likely benign (0.1185); Common (popmax 9.61%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about LYPLA1 p.Pro153Ser (c.457C>T)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

LYPLA1 p.Pro153Ser

Q: How common is LYPLA1 p.Pro153Ser (c.457C>T) in the general population?

LYPLA1 p.Pro153Ser (c.457C>T) is common (popmax 9.61%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.457C>T · rs11549448 · VCV783525

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.61%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.55	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 2.8	phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 15 kb · p 6.8e-08 · regional, not allelic
Overall
CADD	16.05	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 9.61% African / African-American · 7,197/74,884 alleles

Filtering AF 9.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.35%

Overall 0.503% 8,115/1,612,002 alleles · common exomes 4,067/1,459,788 · genomes 4,048/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.61%	10
Remaining individualsnot grpmax-eligible	0.619%	162
Middle Eastern	0.582%	172
Admixed American	0.537%	186
South Asian	0.0297%	3,371
European (non-Finnish)	0.0126%	7,911
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,580

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: LYPLA1
Protein: p.Pro153Ser
Coding: c.457C>T
MANE Select: NM_006330
dbSNP: rs11549448
Type: single nucleotide variant
Location: chr8:54052660 (GRCh38)
Gene constraint: LOEUF 1.56 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.71 · 6 PDB
Residue 153: a UniProt-annotated variant site (in)

Full LYPLA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LYPLA1 p.Ala141Gly Uncertain significance ★ ⚠ same type
LYPLA1 p.Arg149Trp Uncertain significance ★ ⚠ same type
LYPLA1 p.Gln168His Uncertain significance ★ ⚠ same type
LYPLA1 p.Glu103Val Uncertain significance ★ ⚠ same type
LYPLA1 p.His170Leu Uncertain significance ★ ⚠ same type
LYPLA1 p.Ile108Val Uncertain significance ★ ⚠ same type
LYPLA1 p.Ile49Thr Uncertain significance ★ ⚠ same type
LYPLA1 p.Ile49Val 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/lypla1-p-pro153ser (accessed [today's date]).

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