Is PDF p.Pro62Ala (c.184C>G) pathogenic?

PDF p.Pro62Ala (c.184C>G) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.1514); Ultra-rare (popmax 0.0356%, sas).

How common is PDF p.Pro62Ala (c.184C>G) in the general population?

PDF p.Pro62Ala (c.184C>G) is ultra-rare (popmax 0.0356%, sas) (gnomAD).

What do computational predictors say about PDF p.Pro62Ala (c.184C>G)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

PDF p.Pro62Ala

c.184C>G · rs772284121 · VCV2543780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

⚠ 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	0.1514	likely benign
REVEL	0.338	indeterminate
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	23.9	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 0.0356% South Asian · 28/78,668 alleles

Filtering AF 0.0252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0218%

Overall 0.00284% 42/1,479,382 alleles · ultra-rare exomes 40/1,327,420 · genomes 2/151,962 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0356%	2,810
Remaining individualsnot grpmax-eligible	0.0035%	28,591
European (non-Finnish)	0.00107%	93,584

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.Pro62Ala
Coding: c.184C>G
MANE Select: NM_022341
dbSNP: rs772284121
Type: single nucleotide variant
Location: chr16:69330387 (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-pro62ala (accessed [today's date]).

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