Is LIPC p.Ser91= (c.273G>A) pathogenic?

LIPC p.Ser91= (c.273G>A) is classified Uncertain significance in LIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-23). Very rare (popmax 0.00704%, nfe).

How common is LIPC p.Ser91= (c.273G>A) in the general population?

LIPC p.Ser91= (c.273G>A) is very rare (popmax 0.00704%, nfe) (gnomAD).

LIPC p.Ser91=

c.273G>A · rs143786281 · VCV2899873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00704%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.93	donor loss · deltas
Pangolin	Δ0.67	loss · gain 0.42 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 4.5, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00704% European (non-Finnish) · 83/1,179,804 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00601% 97/1,613,790 alleles · very rare exomes 88/1,461,622 · genomes 9/152,168 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,413
European (non-Finnish)grpmax	0.00704%	14,214
Admixed American	0.00666%	15,004
East Asian	0.00446%	22,432
South Asian	0.0022%	45,529

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser91=
Coding: c.273G>A
MANE Select: NM_000236
dbSNP: rs143786281
Type: single nucleotide variant
Location: chr15:58538517 (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

Similar variants

LIPC p.Ser91Leu Uncertain significance ★ ⚠ same residue
LIPC c.456+2T>C Uncertain significance ★★ same type
LIPC c.456+5C>T Uncertain significance ★★ same type
LIPC p.Ala105Val Uncertain significance ★★ ⚠ same type
LIPC p.Ala106Val Uncertain significance ★★ ⚠ same type
LIPC p.Arg135Cys Uncertain significance ★★ ⚠ same type
LIPC p.Arg135His Uncertain significance ★★ ⚠ same type
LIPC p.Arg138Cys 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/lipc-p-ser91 (accessed [today's date]).

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