Is LPL p.Phe297= (c.891T>C) pathogenic?

LPL p.Phe297= (c.891T>C) is classified Likely benign in LPL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-07). Very rare (popmax 0.00178%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LPL p.Phe297= (c.891T>C)?

LPL p.Phe297= (c.891T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is LPL p.Phe297= (c.891T>C) in the general population?

LPL p.Phe297= (c.891T>C) is very rare (popmax 0.00178%, nfe) (gnomAD).

LPL p.Phe297=

c.891T>C · rs150120283 · VCV1109601

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Conditions

Cardiovascular phenotype

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 0.47	GERP -2.4, phastCons 1
Overall
CADD	7.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,180,012 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00143% 23/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,191
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,914

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: LPL
Protein: p.Phe297=
Coding: c.891T>C
MANE Select: NM_000237
dbSNP: rs150120283
Type: single nucleotide variant
Location: chr8:19955956 (GRCh38)
Gene constraint: LOEUF 1.075 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 5 PDB
Residue 297: an α-helix; a disulfide bond; a UniProt-annotated variant site (in hlpp1 and hyperlipidemia; synthesized as a catalytically inactive form; total amount is almost equal to that of the normal enzyme; non-releasable by heparin due to the abnormal structure of the mutant protein)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LPL p.Phe297Ser Uncertain significance ★ ⚠ same residue
LPL c.1019-2A>T Pathogenic ★★ same condition
LPL c.1139+1G>A Likely pathogenic ★★ same condition
LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same condition
LPL c.249+1G>A Pathogenic ★★ same condition
LPL p.Ala98Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
LPL p.Arg197Cys Likely pathogenic ★★ ⚠ same condition
LPL p.Asp277Asn Pathogenic/Likely pathogenic ★★ 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/lpl-p-phe297 (accessed [today's date]).

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