Is PDF p.Pro90Arg (c.269C>G) pathogenic?

PDF p.Pro90Arg (c.269C>G) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1111); Rare (popmax 0.135%, sas).

How common is PDF p.Pro90Arg (c.269C>G) in the general population?

PDF p.Pro90Arg (c.269C>G) is rare (popmax 0.135%, sas) (gnomAD).

What do computational predictors say about PDF p.Pro90Arg (c.269C>G)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

PDF p.Pro90Arg

c.269C>G · VCV4830838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.135%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% South Asian · 95/70,604 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.00691% 99/1,433,228 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.135%	743
Remaining individualsnot grpmax-eligible	0.00544%	18,395
African / African-American	0.00149%	66,970

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.Pro90Arg
Coding: c.269C>G
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69330302 (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-pro90arg (accessed [today's date]).

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