Is LIPC p.Pro438= (c.1314A>G) pathogenic?

LIPC p.Pro438= (c.1314A>G) is classified Benign/Likely benign in LIPC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). Rare (popmax 0.78%, afr); Associated with hyperlipidemia due to hepatic triglyceride lipase deficiency.

What condition is associated with LIPC p.Pro438= (c.1314A>G)?

LIPC p.Pro438= (c.1314A>G) is associated with hyperlipidemia due to hepatic triglyceride lipase deficiency (ClinVar).

How common is LIPC p.Pro438= (c.1314A>G) in the general population?

LIPC p.Pro438= (c.1314A>G) is rare (popmax 0.78%, afr) (gnomAD).

LIPC p.Pro438=

Q: How is Hyperlipidemia due to hepatic triacylglycerol lipase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1314A>G · rs75983069 · VCV885173

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.78%, afr)

Conditions

hyperlipidemia due to hepatic triglyceride lipase deficiency

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 -14	GERP -9.6
Overall
CADD	0.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.78% African / African-American · 585/75,038 alleles

Filtering AF 0.727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.707%

Overall 0.0383% 619/1,614,164 alleles · rare exomes 313/1,461,848 · genomes 306/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.78%	128
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Middle Eastern	0.0166%	6,036
Admixed American	0.01%	10,005
South Asian	0.0011%	91,082
European (non-Finnish)	0.000169%	590,016

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: LIPC
Protein: p.Pro438=
Coding: c.1314A>G
MANE Select: NM_000236
dbSNP: rs75983069
Type: single nucleotide variant
Location: chr15:58563649 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03
Residue 438: the plat domain

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

Disease context

hyperlipidemia due to hepatic triglyceride lipase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hyperlipidemia due to hepatic triacylglycerol lipase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: No data available

Similar variants

LIPC p.Pro438Gln Uncertain significance ★ ⚠ same residue
LIPC c.456+2T>C Uncertain significance ★★ same condition
LIPC c.456+5C>T Uncertain significance ★★ same condition
LIPC p.Ala105Val Uncertain significance ★★ ⚠ same condition
LIPC p.Ala106Val Uncertain significance ★★ ⚠ same condition
LIPC p.Arg135Cys Uncertain significance ★★ ⚠ same condition
LIPC p.Arg225Gln Uncertain significance ★★ ⚠ same condition
LIPC p.Arg329His 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/lipc-p-pro438 (accessed [today's date]).

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