Is PDF p.Pro90Thr (c.268C>A) pathogenic?

PDF p.Pro90Thr (c.268C>A) is classified Benign in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). AlphaMissense: likely benign (0.1104); Low-frequency (popmax 1.07%, sas).

How common is PDF p.Pro90Thr (c.268C>A) in the general population?

PDF p.Pro90Thr (c.268C>A) is low-frequency (popmax 1.07%, sas) (gnomAD).

What do computational predictors say about PDF p.Pro90Thr (c.268C>A)?

AlphaMissense predicts likely benign (score 0.1104) — an in-silico prediction, not a clinical call.

PDF p.Pro90Thr

c.268C>A · VCV4083854

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1104 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1104	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -9.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	21.4	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 1.07% South Asian · 755/70,620 alleles

Filtering AF 1.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.981%

Overall 0.0561% 804/1,433,300 alleles · low-frequency exomes 745/1,281,260 · genomes 59/152,040 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.07%	94
Remaining individualsnot grpmax-eligible	0.0652%	1,533
Middle Eastern	0.0461%	2,170
East Asian	0.00304%	32,930
African / African-American	0.00299%	33,492
Admixed American	0.00298%	33,554
European (non-Finnish)	0.000635%	157,498

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.Pro90Thr
Coding: c.268C>A
MANE Select: NM_022341
Type: single nucleotide variant
Location: chr16:69330303 (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-pro90thr (accessed [today's date]).

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