Is LIPT2 p.Pro39Ser (c.115C>T) pathogenic?

LIPT2 p.Pro39Ser (c.115C>T) is classified Likely benign in LIPT2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-02). AlphaMissense: likely benign (0.0835); Rare (popmax 0.292%, sas).

How common is LIPT2 p.Pro39Ser (c.115C>T) in the general population?

LIPT2 p.Pro39Ser (c.115C>T) is rare (popmax 0.292%, sas) (gnomAD).

What do computational predictors say about LIPT2 p.Pro39Ser (c.115C>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

LIPT2 p.Pro39Ser

c.115C>T · rs570309441 · VCV3058612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.292%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -5.51	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 0.19	GERP -3, phastCons 0.003
Regional constraint	o/e 1.22	unconstrained · MANE · 1,565 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	5.18	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

Grpmax group 0.292% South Asian · 218/74,628 alleles

Filtering AF 0.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.248%

Overall 0.0161% 234/1,453,912 alleles · rare exomes 221/1,301,640 · genomes 13/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.292%	342
Remaining individualsnot grpmax-eligible	0.0232%	4,310
African / African-American	0.00147%	67,886
European (non-Finnish)	0.00018%	554,250

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.Pro39Ser
Coding: c.115C>T
MANE Select: NM_001144869
dbSNP: rs570309441
Type: single nucleotide variant
Location: chr11:74493589 (GRCh38)
Gene constraint: LOEUF 1.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.37

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-pro39ser (accessed [today's date]).

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