Is PDGFRB p.Pro154Arg (c.461C>G) pathogenic?

PDGFRB p.Pro154Arg (c.461C>G) is classified Uncertain significance in PDGFRB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-03). AlphaMissense: likely pathogenic (0.627); Very rare (popmax 0.00195%, nfe); Associated with basal ganglia calcification, idiopathic, 4.

How common is PDGFRB p.Pro154Arg (c.461C>G) in the general population?

PDGFRB p.Pro154Arg (c.461C>G) is very rare (popmax 0.00195%, nfe) (gnomAD).

How is Bilateral striopallidodentate calcinosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PDGFRB p.Pro154Arg (c.461C>G)?

AlphaMissense predicts likely pathogenic (score 0.627) — an in-silico prediction, not a clinical call.

PDGFRB p.Pro154Arg

Q: What condition is associated with PDGFRB p.Pro154Arg (c.461C>G)?

PDGFRB p.Pro154Arg (c.461C>G) is associated with basal ganglia calcification, idiopathic, 4, acroosteolysis-keloid-like lesions-premature aging syndrome, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (ClinVar).

c.461C>G · rs774900944 · VCV2933154

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

basal ganglia calcification, idiopathic, 4

Computational evidence

Protein change
AlphaMissense	0.627	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	28.6	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 0.00195% European (non-Finnish) · 23/1,179,610 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00157% 23/1,461,384 alleles · very rare

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: PDGFRB
Protein: p.Pro154Arg
Coding: c.461C>G
MANE Select: NM_002609
dbSNP: rs774900944
Type: single nucleotide variant
Location: chr5:150134920 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 154: a disulfide bond; the ig-like c2-type 2 domain

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

Disease context

basal ganglia calcification, idiopathic, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acroosteolysis-keloid-like lesions-premature aging syndrome skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome infantile myofibromatosis

For Bilateral striopallidodentate calcinosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Adult

Similar variants

PDGFRB p.Pro154Ser Uncertain significance ★ ⚠ same residue
PDGFRB p.Pro154= Likely benign ★ same residue
PDGFRB p.Arg561Cys Pathogenic ★★ ⚠ same condition
PDGFRB p.Asn666His Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Asn666Lys Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Asn666Ser Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Pro560Leu Pathogenic/Likely pathogenic ★★ same condition
PDGFRB p.Pro584Arg Pathogenic ★★ 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/pdgfrb-p-pro154arg (accessed [today's date]).

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