Is LIPC p.Ala196= (c.588G>A) pathogenic?

LIPC p.Ala196= (c.588G>A) is classified Conflicting classifications of pathogenicity in LIPC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-14). Rare (popmax 0.385%, amr); Associated with hyperlipidemia due to hepatic triglyceride lipase deficiency.

What condition is associated with LIPC p.Ala196= (c.588G>A)?

LIPC p.Ala196= (c.588G>A) is associated with hyperlipidemia due to hepatic triglyceride lipase deficiency (ClinVar).

How common is LIPC p.Ala196= (c.588G>A) in the general population?

LIPC p.Ala196= (c.588G>A) is rare (popmax 0.385%, amr) (gnomAD).

LIPC p.Ala196=

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.588G>A · rs34351746 · VCV316663

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.385%, amr)

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 -16	GERP -9.6
Overall
CADD	0.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.385% Admixed American · 231/60,026 alleles

Filtering AF 0.344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.328%

Overall 0.147% 2,369/1,614,116 alleles · rare exomes 2,166/1,461,808 · genomes 203/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.385%	260
Ashkenazi Jewishnot grpmax-eligible	0.28%	357
European (non-Finnish)	0.157%	636
Remaining individualsnot grpmax-eligible	0.154%	651
South Asian	0.0867%	1,153
Middle Eastern	0.033%	3,028
African / African-American	0.024%	4,169
East Asian	0.00669%	14,958
Finnishnot grpmax-eligible	0.00156%	64,028

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.Ala196=
Coding: c.588G>A
MANE Select: NM_000236
dbSNP: rs34351746
Type: single nucleotide variant
Location: chr15:58545755 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03

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.Ala196Thr Uncertain significance ★ ⚠ same residue
LIPC p.Ala196Val 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

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-ala196 (accessed [today's date]).

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