Is LIPT2 p.Pro67Arg (c.200C>G) pathogenic?

LIPT2 p.Pro67Arg (c.200C>G) is classified Uncertain significance in LIPT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.092); Ultra-rare (popmax 0.0313%, amr).

How common is LIPT2 p.Pro67Arg (c.200C>G) in the general population?

LIPT2 p.Pro67Arg (c.200C>G) is ultra-rare (popmax 0.0313%, amr) (gnomAD).

What do computational predictors say about LIPT2 p.Pro67Arg (c.200C>G)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

LIPT2 p.Pro67Arg

c.200C>G · rs1046467978 · VCV1991031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0313%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.1	GERP 1.5, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 1,565 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.0313% Admixed American · 11/35,126 alleles

Filtering AF 0.0175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.000768% 11/1,432,250 alleles · ultra-rare exomes 9/1,280,004 · genomes 2/152,246 · 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.Pro67Arg
Coding: c.200C>G
MANE Select: NM_001144869
dbSNP: rs1046467978
Type: single nucleotide variant
Location: chr11:74493504 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37
Residue 67: the bpl/lpl catalytic domain

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

Similar variants

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
LIPT2 p.Glu207Lys Uncertain significance ★★ ⚠ same type
LIPT2 p.Gly109Asp 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-pro67arg (accessed [today's date]).

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