Is LIPT2 p.Phe91= (c.273C>T) pathogenic?

LIPT2 p.Phe91= (c.273C>T) is classified Benign/Likely benign in LIPT2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-13). Rare (popmax 0.395%, amr); Associated with encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities.

How common is LIPT2 p.Phe91= (c.273C>T) in the general population?

LIPT2 p.Phe91= (c.273C>T) is rare (popmax 0.395%, amr) (gnomAD).

LIPT2 p.Phe91=

Q: What condition is associated with LIPT2 p.Phe91= (c.273C>T)?

LIPT2 p.Phe91= (c.273C>T) is associated with encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities (ClinVar).

c.273C>T · rs192239391 · VCV1601557

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.395%, amr)

Conditions

encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities

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 2.3	GERP -2.8, phastCons 1
Overall
CADD	15.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.395% Admixed American · 189/47,876 alleles

Filtering AF 0.349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.0131% 198/1,505,956 alleles · rare exomes 176/1,353,630 · genomes 22/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.395%	253
Remaining individualsnot grpmax-eligible	0.00852%	11,734
African / African-American	0.00288%	34,698
East Asian	0.00269%	37,230
European (non-Finnish)	8.82e-05%	1,134,330

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.Phe91=
Coding: c.273C>T
MANE Select: NM_001144869
dbSNP: rs192239391
Type: single nucleotide variant
Location: chr11:74493431 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37
Residue 91: the bpl/lpl catalytic domain; a binding site

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

Disease context

encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIPT2 p.Gly109Asp Uncertain significance ★★ ⚠ same condition
LIPT2 p.Gly95Asp Uncertain significance ★★ ⚠ same condition
LIPT2 p.Ile36Thr Uncertain significance ★★ ⚠ same condition
LIPT2 c.466+14A>C Benign ★★ same condition
LIPT2 p.Leu8= Benign ★★ same condition
LIPT2 p.Pro230= Benign/Likely benign ★★ same condition
LIPT2 p.Thr190Ser Benign ★★ same condition
LIPT2 p.Met1Leu Likely pathogenic ★ 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/lipt2-p-phe91 (accessed [today's date]).

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