Is PDF p.Ala7Ser (c.19G>T) pathogenic?

PDF p.Ala7Ser (c.19G>T) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.0998); Very rare (popmax 0.00754%, amr).

How common is PDF p.Ala7Ser (c.19G>T) in the general population?

PDF p.Ala7Ser (c.19G>T) is very rare (popmax 0.00754%, amr) (gnomAD).

What do computational predictors say about PDF p.Ala7Ser (c.19G>T)?

AlphaMissense predicts likely benign (score 0.0998) — an in-silico prediction, not a clinical call.

PDF p.Ala7Ser

c.19G>T · rs1172324284 · VCV2288766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00754%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0998	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.9	GERP -3.1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	0.066	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 0.00754% Admixed American · 3/39,770 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00034% 5/1,469,598 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00754%	13,257
South Asian	0.00131%	76,510
European (non-Finnish)	8.93e-05%	1,120,062

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.Ala7Ser
Coding: c.19G>T
MANE Select: NM_032382 · reported on NM_022341
dbSNP: rs1172324284
Type: single nucleotide variant
Location: chr16:69330552 (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-ala7ser (accessed [today's date]).

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