Is PDGFRB p.Arg439Pro (c.1316G>C) pathogenic?

PDGFRB p.Arg439Pro (c.1316G>C) is classified Uncertain significance in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-24). AlphaMissense: likely pathogenic (0.9764); Absent from gnomAD v4.1.

How common is PDGFRB p.Arg439Pro (c.1316G>C) in the general population?

PDGFRB p.Arg439Pro (c.1316G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRB p.Arg439Pro (c.1316G>C)?

AlphaMissense predicts likely pathogenic (score 0.9764) — an in-silico prediction, not a clinical call.

PDGFRB p.Arg439Pro

c.1316G>C · rs746042729 · VCV1698226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9764 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9764	likely pathogenic
REVEL	0.334	indeterminate
SaProt	LLR -16.07	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.86, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Arg439Pro
Coding: c.1316G>C
MANE Select: NM_002609
dbSNP: rs746042729
Type: single nucleotide variant
Location: chr5:150130590 (GRCh38)
Gene constraint: LOEUF 0.504 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 72.96 · 9 PDB
Residue 439: a disulfide bond; the ig-like c2-type 5 domain

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

Similar variants

PDGFRB p.Arg561Cys Pathogenic ★★ ⚠ same type
PDGFRB p.Asn666His Pathogenic/Likely pathogenic ★★ same type
PDGFRB p.Asn666Lys Pathogenic/Likely pathogenic ★★ same type
PDGFRB p.Asn666Ser Pathogenic/Likely pathogenic ★★ ⚠ same type
PDGFRB p.Pro560Leu Pathogenic/Likely pathogenic ★★ same type
PDGFRB p.Pro584Arg Pathogenic ★★ same type
PDGFRB p.Trp566Arg Pathogenic ★★ same type
PDGFRB p.Ala513Thr Uncertain significance ★★ ⚠ same type

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-arg439pro (accessed [today's date]).

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