Is PDF p.Leu52Pro (c.155T>C) pathogenic?

PDF p.Leu52Pro (c.155T>C) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: ambiguous (0.4762); Ultra-rare (popmax 0.0153%, sas).

How common is PDF p.Leu52Pro (c.155T>C) in the general population?

PDF p.Leu52Pro (c.155T>C) is ultra-rare (popmax 0.0153%, sas) (gnomAD).

What do computational predictors say about PDF p.Leu52Pro (c.155T>C)?

AlphaMissense predicts ambiguous (score 0.4762) — an in-silico prediction, not a clinical call.

PDF p.Leu52Pro

c.155T>C · VCV3305443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4762 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.4762	ambiguous
REVEL	0.079	moderately benign-leaning
SaProt	LLR -13.96	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 0.79
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	21.7	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 0.0153% South Asian · 12/78,394 alleles

Filtering AF 0.00874% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00115% 17/1,476,886 alleles · ultra-rare exomes 16/1,325,028 · genomes 1/151,858 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0153%	6,533
Remaining individualsnot grpmax-eligible	0.00351%	28,515
European (non-Finnish)	0.000267%	373,980

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.Leu52Pro
Coding: c.155T>C
MANE Select: NM_022341
Type: single nucleotide variant
Location: chr16:69330416 (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-leu52pro (accessed [today's date]).

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