Is LIPE p.Pro985Leu (c.2954C>T) pathogenic?

LIPE p.Pro985Leu (c.2954C>T) is classified Uncertain significance in LIPE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: ambiguous (0.3527); No allele count reported in gnomAD v4.1 (AN 1,494,872); Associated with Inborn genetic diseases.

What condition is associated with LIPE p.Pro985Leu (c.2954C>T)?

LIPE p.Pro985Leu (c.2954C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LIPE p.Pro985Leu (c.2954C>T) in the general population?

LIPE p.Pro985Leu (c.2954C>T) is no allele count reported in gnomAD v4.1 (AN 1,494,872) (gnomAD).

What do computational predictors say about LIPE p.Pro985Leu (c.2954C>T)?

AlphaMissense predicts ambiguous (score 0.3527) — an in-silico prediction, not a clinical call.

LIPE p.Pro985Leu

c.2954C>T · rs1297128310 · VCV2325215

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3527 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,494,872)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3527	ambiguous
REVEL	0.422	indeterminate
SaProt	LLR -11.91	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.019 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,494,872). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LIPE
Protein: p.Pro985Leu
Coding: c.2954C>T
MANE Select: NM_005357
dbSNP: rs1297128310
Type: single nucleotide variant
Location: chr19:42402620 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB
Residue 985: an α-helix

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.Pro985Ser Uncertain significance ★ ⚠ same residue
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

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-pro985leu (accessed [today's date]).

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