Is PDF p.Pro18Leu (c.53C>T) pathogenic?

PDF p.Pro18Leu (c.53C>T) is classified Likely benign in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.0243%, amr).

How common is PDF p.Pro18Leu (c.53C>T) in the general population?

PDF p.Pro18Leu (c.53C>T) is ultra-rare (popmax 0.0243%, amr) (gnomAD).

What do computational predictors say about PDF p.Pro18Leu (c.53C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

PDF p.Pro18Leu

c.53C>T · rs1022004544 · VCV3210817

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.58	GERP -2.9
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	0.397	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 0.0243% Admixed American · 10/41,078 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.00244% 36/1,473,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0243%	4,108
African / African-American	0.00884%	11,314
Remaining individualsnot grpmax-eligible	0.00703%	14,225
Finnishnot grpmax-eligible	0.00461%	21,695
East Asian	0.00292%	34,198
European (non-Finnish)	0.00116%	86,246

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.Pro18Leu
Coding: c.53C>T
MANE Select: NM_032382 · reported on NM_022341
dbSNP: rs1022004544
Type: single nucleotide variant
Location: chr16:69330518 (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-pro18leu (accessed [today's date]).

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