Is PDGFRB p.Pro796Ser (c.2386C>T) pathogenic?

PDGFRB p.Pro796Ser (c.2386C>T) is classified Uncertain significance in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: likely benign (0.0935); Absent from gnomAD v4.1; Associated with acroosteolysis-keloid-like lesions-premature aging syndrome.

What condition is associated with PDGFRB p.Pro796Ser (c.2386C>T)?

PDGFRB p.Pro796Ser (c.2386C>T) is associated with acroosteolysis-keloid-like lesions-premature aging syndrome, basal ganglia calcification, idiopathic, 4, skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome (ClinVar).

How common is PDGFRB p.Pro796Ser (c.2386C>T) in the general population?

PDGFRB p.Pro796Ser (c.2386C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRB p.Pro796Ser (c.2386C>T)?

AlphaMissense predicts likely benign (score 0.0935) — an in-silico prediction, not a clinical call.

PDGFRB p.Pro796Ser

Q: How is Acroosteolysis-keloid-like lesions-premature aging syndrome inherited?

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

c.2386C>T · rs1760125881 · VCV2928117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

acroosteolysis-keloid-like lesions-premature aging syndrome

Computational evidence

Protein change
AlphaMissense	0.0935	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.95, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	22.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDGFRB
Protein: p.Pro796Ser
Coding: c.2386C>T
MANE Select: NM_002609
dbSNP: rs1760125881
Type: single nucleotide variant
Location: chr5:150121281 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 796: the protein kinase domain

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

Disease context

acroosteolysis-keloid-like lesions-premature aging syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: basal ganglia calcification, idiopathic, 4 skeletal overgrowth-craniofacial dysmorphism-hyperelastic skin-white matter lesions syndrome infantile myofibromatosis

For Acroosteolysis-keloid-like lesions-premature aging syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

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
PDGFRB p.Ala513Thr 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/pdgfrb-p-pro796ser (accessed [today's date]).

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