Is PDGFRB p.Arg2Gln (c.5G>A) pathogenic?

PDGFRB p.Arg2Gln (c.5G>A) is classified Conflicting classifications of pathogenicity in PDGFRB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-20). AlphaMissense: likely benign (0.0766); Ultra-rare (popmax 0.0107%, afr); Associated with basal ganglia calcification, idiopathic, 4.

How common is PDGFRB p.Arg2Gln (c.5G>A) in the general population?

PDGFRB p.Arg2Gln (c.5G>A) is ultra-rare (popmax 0.0107%, afr) (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.Arg2Gln (c.5G>A)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

PDGFRB p.Arg2Gln

Q: What condition is associated with PDGFRB p.Arg2Gln (c.5G>A)?

PDGFRB p.Arg2Gln (c.5G>A) 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.5G>A · rs372399976 · VCV3210845

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

basal ganglia calcification, idiopathic, 4

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.97	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 -5.3	GERP -4.2
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	0.735	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 0.0107% African / African-American · 8/74,916 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00161% 26/1,613,460 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,365
South Asian	0.0022%	45,484
Admixed American	0.00167%	59,960
European (non-Finnish)	0.00127%	78,646

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.Arg2Gln
Coding: c.5G>A
MANE Select: NM_002609
dbSNP: rs372399976
Type: single nucleotide variant
Location: chr5:150137043 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB

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.Arg2Trp 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
PDGFRB p.Trp566Arg 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-arg2gln (accessed [today's date]).

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