Is PDGFB p.Pro219Arg (c.656C>G) pathogenic?

PDGFB p.Pro219Arg (c.656C>G) is classified Uncertain significance in PDGFB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.0887); Ultra-rare (popmax 0.0173%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PDGFB p.Pro219Arg (c.656C>G)?

PDGFB p.Pro219Arg (c.656C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PDGFB p.Pro219Arg (c.656C>G) in the general population?

PDGFB p.Pro219Arg (c.656C>G) is ultra-rare (popmax 0.0173%, nfe) (gnomAD).

What do computational predictors say about PDGFB p.Pro219Arg (c.656C>G)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

PDGFB p.Pro219Arg

c.656C>G · rs200444646 · VCV2352264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -4.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 18 kb · p 0.021 · regional, not allelic
Overall
CADD	20.7	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 0.0173% European (non-Finnish) · 204/1,180,006 alleles

Filtering AF 0.0153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0134% 216/1,614,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0173%	5,784
Finnishnot grpmax-eligible	0.0156%	6,403
Remaining individualsnot grpmax-eligible	0.0016%	62,506
African / African-American	0.00133%	75,054

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: PDGFB
Protein: p.Pro219Arg
Coding: c.656C>G
MANE Select: NM_002608
dbSNP: rs200444646
Type: single nucleotide variant
Location: chr22:39225793 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.77 · 6 PDB
Residue 219: the 'disordered' region

Full PDGFB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDGFB p.Pro219= Likely benign ★★ same residue
PDGFB p.Pro219Leu Uncertain significance ★ ⚠ same residue
PDGFB p.Ala6Val Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg142Cys Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg160Trp Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg187Gln Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg187Trp Uncertain significance ★★ ⚠ same condition
PDGFB p.Arg207Gln Uncertain significance ★★ ⚠ same condition

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/pdgfb-p-pro219arg (accessed [today's date]).

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