Is LIPC p.Pro82Ser (c.244C>T) pathogenic?

LIPC p.Pro82Ser (c.244C>T) is classified Uncertain significance in LIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.2242); Absent from gnomAD v4.1.

How common is LIPC p.Pro82Ser (c.244C>T) in the general population?

LIPC p.Pro82Ser (c.244C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LIPC p.Pro82Ser (c.244C>T)?

AlphaMissense predicts likely benign (score 0.2242) — an in-silico prediction, not a clinical call.

LIPC p.Pro82Ser

c.244C>T · VCV4541953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2242 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2242	likely benign
REVEL	0.733	pathogenic-leaning
SaProt	LLR -9.71	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 4.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 137 kb · p 0.056 · regional, not allelic
Overall
CADD	26.9	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

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: LIPC
Protein: p.Pro82Ser
Coding: c.244C>T
MANE Select: NM_000236
Type: single nucleotide variant
Location: chr15:58538488 (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 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
LIPC p.Arg225Gln 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-pro82ser (accessed [today's date]).

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