Is LIPE p.Asp799His (c.2395G>C) pathogenic?

LIPE p.Asp799His (c.2395G>C) is classified Uncertain significance in LIPE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1147); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LIPE p.Asp799His (c.2395G>C)?

LIPE p.Asp799His (c.2395G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LIPE p.Asp799His (c.2395G>C) in the general population?

LIPE p.Asp799His (c.2395G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LIPE p.Asp799His (c.2395G>C)?

AlphaMissense predicts likely benign (score 0.1147) — an in-silico prediction, not a clinical call.

LIPE p.Asp799His

c.2395G>C · rs2040142007 · VCV3119047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1147 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1147	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.74	phastCons 0.2
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.019 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LIPE
Protein: p.Asp799His
Coding: c.2395G>C
MANE Select: NM_005357
dbSNP: rs2040142007
Type: single nucleotide variant
Location: chr19:42405532 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIPE p.Gln150Glu Uncertain significance ★★ ⚠ same condition
LIPE p.Leu777Phe Uncertain significance ★★ ⚠ same condition
LIPE p.Asn499= Likely benign ★★ same condition
LIPE p.Gly445= Likely benign ★★ same condition
LIPE p.Ala1055Ser Uncertain significance ★ ⚠ same condition
LIPE p.Ala159Thr Uncertain significance ★ ⚠ same condition
LIPE p.Ala345Val Uncertain significance ★ ⚠ same condition
LIPE p.Ala351Val 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-asp799his (accessed [today's date]).

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