Is PDF p.Ala7= (c.21G>A) pathogenic?

PDF p.Ala7= (c.21G>A) is classified Likely benign in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Very rare (popmax 0.00695%, nfe).

How common is PDF p.Ala7= (c.21G>A) in the general population?

PDF p.Ala7= (c.21G>A) is very rare (popmax 0.00695%, nfe) (gnomAD).

PDF p.Ala7=

c.21G>A · VCV4821641

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.092	GERP -0.51
Overall
CADD	6.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% European (non-Finnish) · 78/1,121,616 alleles

Filtering AF 0.00566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00524%

Overall 0.00563% 83/1,474,314 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,380
Remaining individualsnot grpmax-eligible	0.00351%	28,477
East Asian	0.00287%	34,810
Finnishnot grpmax-eligible	0.0023%	43,386
African / African-American	0.00148%	67,632

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.Ala7=
Coding: c.21G>A
MANE Select: NM_032382 · reported on NM_022341
Type: single nucleotide variant
Location: chr16:69330550 (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-ala7 (accessed [today's date]).

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