Is LIPE p.Glu833= (c.2499G>A) pathogenic?

LIPE p.Glu833= (c.2499G>A) is classified Likely benign in LIPE (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-18). Ultra-rare (popmax 0.0637%, sas); Associated with LIPE-related disorder.

What condition is associated with LIPE p.Glu833= (c.2499G>A)?

LIPE p.Glu833= (c.2499G>A) is associated with LIPE-related disorder (ClinVar).

How common is LIPE p.Glu833= (c.2499G>A) in the general population?

LIPE p.Glu833= (c.2499G>A) is ultra-rare (popmax 0.0637%, sas) (gnomAD).

LIPE p.Glu833=

c.2499G>A · VCV3350619

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0637%, sas)

Conditions

LIPE-related disorder

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 0.5	phastCons 1
Overall
CADD	7.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0637% South Asian · 58/91,066 alleles

Filtering AF 0.0505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0458%

Overall 0.00397% 64/1,613,838 alleles · ultra-rare exomes 63/1,461,632 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0637%	1,570
Middle Eastern	0.0168%	5,936
Remaining individualsnot grpmax-eligible	0.0048%	20,823
European (non-Finnish)	0.000169%	590,009

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: LIPE
Protein: p.Glu833=
Coding: c.2499G>A
MANE Select: NM_005357
Type: single nucleotide variant
Location: chr19:42405428 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB

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

Disease context

LIPE-related disorder

Similar variants

LIPE p.Arg821Cys Uncertain significance ★★ ⚠ same condition
LIPE p.Glu688Ter Likely pathogenic ★ same condition
LIPE c.-32G>C Uncertain significance ★ same condition
LIPE p.Asp582Asn Uncertain significance ⚠ same condition
LIPE c.2968-9G>C Likely benign same condition
LIPE p.Ala1030= Likely benign same condition
LIPE p.Pro21= Likely benign same condition
LIPE p.Leu913fs 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/lipe-p-glu833 (accessed [today's date]).

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