Is PDF p.Val152Met (c.454G>A) pathogenic?

PDF p.Val152Met (c.454G>A) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-19). AlphaMissense: ambiguous (0.4729); Very rare (popmax 0.00525%, amr).

How common is PDF p.Val152Met (c.454G>A) in the general population?

PDF p.Val152Met (c.454G>A) is very rare (popmax 0.00525%, amr) (gnomAD).

What do computational predictors say about PDF p.Val152Met (c.454G>A)?

AlphaMissense predicts ambiguous (score 0.4729) — an in-silico prediction, not a clinical call.

PDF p.Val152Met

c.454G>A · VCV3416345

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, amr)

Computational evidence

Protein change
AlphaMissense	0.4729	ambiguous
REVEL	0.432	indeterminate
SaProt	LLR -13.27	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	28.5	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 0.00525% Admixed American · 3/57,190 alleles

Filtering AF 0.00147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00124%

Overall 0.00203% 29/1,431,818 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00525%	19,063
European (non-Finnish)	0.00214%	46,715
South Asian	0.00114%	87,602

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.Val152Met
Coding: c.454G>A
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69330117 (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-val152met (accessed [today's date]).

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