Is PDF p.Phe148Cys (c.443T>G) pathogenic?

PDF p.Phe148Cys (c.443T>G) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-16). AlphaMissense: likely pathogenic (0.8201); Very rare (popmax 0.00244%, eas).

How common is PDF p.Phe148Cys (c.443T>G) in the general population?

PDF p.Phe148Cys (c.443T>G) is very rare (popmax 0.00244%, eas) (gnomAD).

What do computational predictors say about PDF p.Phe148Cys (c.443T>G)?

AlphaMissense predicts likely pathogenic (score 0.8201) — an in-silico prediction, not a clinical call.

PDF p.Phe148Cys

c.443T>G · VCV3305439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8201 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.8201	likely pathogenic
REVEL	0.09	moderately benign-leaning
SaProt	LLR -10.81	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
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	24.8	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 0.00244% East Asian · 1/40,936 alleles

Overall 0.000127% 2/1,577,682 alleles · very rare exomes 2/1,425,602 · genomes 0/152,080 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,936
European (non-Finnish)	8.58e-05%	1,165,026

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.Phe148Cys
Coding: c.443T>G
MANE Select: NM_022341
Type: single nucleotide variant
Location: chr16:69330128 (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-phe148cys (accessed [today's date]).

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