Is LIPT2 p.Pro94= (c.282G>C) pathogenic?

LIPT2 p.Pro94= (c.282G>C) is classified Likely benign in LIPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-10). Very rare (popmax 0.000352%, nfe).

How common is LIPT2 p.Pro94= (c.282G>C) in the general population?

LIPT2 p.Pro94= (c.282G>C) is very rare (popmax 0.000352%, nfe) (gnomAD).

LIPT2 p.Pro94=

c.282G>C · rs1329263134 · VCV2976123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000352%, nfe)

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 -12	GERP -2.9
Overall
CADD	3.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000352% European (non-Finnish) · 4/1,135,988 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.6e-05%

Overall 0.000265% 4/1,509,358 alleles · very rare exomes 2/1,357,144 · genomes 2/152,214 · joint denominator

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: LIPT2
Protein: p.Pro94=
Coding: c.282G>C
MANE Select: NM_001144869
dbSNP: rs1329263134
Type: single nucleotide variant
Location: chr11:74493422 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37
Residue 94: the bpl/lpl catalytic domain

Full LIPT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LIPT2 p.Pro94Leu Uncertain significance ★ ⚠ same residue
LIPT2 p.Pro94Ser Uncertain significance ★ ⚠ same residue
LIPT2 p.Ala121Val Uncertain significance ★★ ⚠ same type
LIPT2 p.Ala75Thr Uncertain significance ★★ ⚠ same type
LIPT2 p.Arg158Cys Uncertain significance ★★ ⚠ same type
LIPT2 p.Arg2Gln Uncertain significance ★★ ⚠ same type
LIPT2 p.Asp134Ala Uncertain significance ★★ ⚠ same type
LIPT2 p.Gln133Glu 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/lipt2-p-pro94 (accessed [today's date]).

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