Is PDF p.Leu142Pro (c.425T>C) pathogenic?

PDF p.Leu142Pro (c.425T>C) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-16). AlphaMissense: likely benign (0.273); Very rare (popmax 0.00285%, afr).

How common is PDF p.Leu142Pro (c.425T>C) in the general population?

PDF p.Leu142Pro (c.425T>C) is very rare (popmax 0.00285%, afr) (gnomAD).

What do computational predictors say about PDF p.Leu142Pro (c.425T>C)?

AlphaMissense predicts likely benign (score 0.273) — an in-silico prediction, not a clinical call.

PDF p.Leu142Pro

c.425T>C · VCV3930151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.273 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00285%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.273	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP 0.67, phastCons 0.006
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	19.63	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 0.00285% African / African-American · 2/70,094 alleles

Filtering AF 0.000628% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000484%

Overall 0.00103% 16/1,553,844 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00285%	35,047
Remaining individualsnot grpmax-eligible	0.00167%	59,788
European (non-Finnish)	0.00113%	88,793

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: PDF
Protein: p.Leu142Pro
Coding: c.425T>C
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69330146 (GRCh38)

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

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/pdf-p-leu142pro (accessed [today's date]).

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