Is PDF p.Leu158Val (c.472C>G) pathogenic?

PDF p.Leu158Val (c.472C>G) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.132); Very rare (popmax 0.000429%, nfe).

How common is PDF p.Leu158Val (c.472C>G) in the general population?

PDF p.Leu158Val (c.472C>G) is very rare (popmax 0.000429%, nfe) (gnomAD).

What do computational predictors say about PDF p.Leu158Val (c.472C>G)?

AlphaMissense predicts likely benign (score 0.132) — an in-silico prediction, not a clinical call.

PDF p.Leu158Val

c.472C>G · VCV3416344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000429%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.132	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -10.52	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 1.5	GERP -1.5, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	18.39	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 0.000429% European (non-Finnish) · 5/1,166,258 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000316% 5/1,581,238 alleles · very rare

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.Leu158Val
Coding: c.472C>G
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69330099 (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-leu158val (accessed [today's date]).

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