Is PDF p.Ser230Arg (c.688A>C) pathogenic?

PDF p.Ser230Arg (c.688A>C) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-09). AlphaMissense: likely pathogenic (0.8023); Ultra-rare (popmax 0.0733%, afr).

How common is PDF p.Ser230Arg (c.688A>C) in the general population?

PDF p.Ser230Arg (c.688A>C) is ultra-rare (popmax 0.0733%, afr) (gnomAD).

What do computational predictors say about PDF p.Ser230Arg (c.688A>C)?

AlphaMissense predicts likely pathogenic (score 0.8023) — an in-silico prediction, not a clinical call.

PDF p.Ser230Arg

c.688A>C · VCV3305438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8023 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0733%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8023	likely pathogenic
REVEL	0.112	moderately benign-leaning
SaProt	LLR -7.44	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.1	GERP -1.1, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	23.3	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 0.0733% African / African-American · 55/75,042 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0522%

Overall 0.00403% 65/1,612,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0733%	1,364
Admixed American	0.015%	6,648
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Ser230Arg
Coding: c.688A>C
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69329066 (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-ser230arg (accessed [today's date]).

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