Is PET100 p.Pro44Leu (c.131C>T) pathogenic?

PET100 p.Pro44Leu (c.131C>T) is classified Uncertain significance in PET100 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-28). AlphaMissense: likely benign (0.1443); Very rare (popmax 0.00411%, afr); Associated with Inborn genetic diseases.

What condition is associated with PET100 p.Pro44Leu (c.131C>T)?

PET100 p.Pro44Leu (c.131C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PET100 p.Pro44Leu (c.131C>T) in the general population?

PET100 p.Pro44Leu (c.131C>T) is very rare (popmax 0.00411%, afr) (gnomAD).

What do computational predictors say about PET100 p.Pro44Leu (c.131C>T)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

PET100 p.Pro44Leu

c.131C>T · VCV3887845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00411%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -10.67	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 1,719 bp · p 0.9 · regional, not allelic
Overall
CADD	24.5	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 0.00411% African / African-American · 3/73,028 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000502%

Overall 0.000195% 3/1,537,118 alleles · very rare exomes 2/1,384,942 · genomes 1/152,176 · 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: PET100
Protein: p.Pro44Leu
Coding: c.131C>T
MANE Select: NM_001171155
Type: single nucleotide variant
Location: chr19:7630839 (GRCh38)
Gene constraint: LOEUF 1.597 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50

Full PET100 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PET100 p.Ala69Ser Uncertain significance ★★ ⚠ same condition
PET100 p.Arg58Gln Uncertain significance ★★ ⚠ same condition
PET100 p.Arg60Trp Uncertain significance ★★ ⚠ same condition
PET100 p.Glu62Val Uncertain significance ★★ ⚠ same condition
PET100 p.Arg37His Uncertain significance ★ ⚠ same condition
PET100 p.Arg39Lys Uncertain significance ★ ⚠ same condition
PET100 p.Arg60Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
PET100 p.Arg67His Conflicting classifications of pathogenicity ★ ⚠ 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/pet100-p-pro44leu (accessed [today's date]).

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