Is PDGFB p.Arg129Cys (c.385C>T) pathogenic?

PDGFB p.Arg129Cys (c.385C>T) is classified Pathogenic in PDGFB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely pathogenic (0.9701); Very rare (popmax 0.00017%, nfe).

How common is PDGFB p.Arg129Cys (c.385C>T) in the general population?

PDGFB p.Arg129Cys (c.385C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PDGFB p.Arg129Cys (c.385C>T)?

AlphaMissense predicts likely pathogenic (score 0.9701) — an in-silico prediction, not a clinical call.

PDGFB p.Arg129Cys

c.385C>T · rs2517761949 · VCV2874449

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9701 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9701	likely pathogenic ✓ concordant with ClinVar · top 7% in PDGFB
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -14.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 18 kb · p 0.021 · regional, not allelic
Overall
CADD	34.0	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 0.00017% European (non-Finnish) · 2/1,176,186 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,451,996 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: PDGFB
Protein: p.Arg129Cys
Coding: c.385C>T
MANE Select: NM_002608
dbSNP: rs2517761949
Type: single nucleotide variant
Location: chr22:39231693 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.77 · 6 PDB
Residue 129: a β-strand; a disulfide bond

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

Similar variants

PDGFB p.Arg129His Uncertain significance ★ ⚠ same residue
PDGFB p.Arg149Ter Pathogenic ★★ same type
PDGFB c.64-5G>A Uncertain significance ★★ same type
PDGFB p.Ala6Val Uncertain significance ★★ ⚠ same type
PDGFB p.Arg142Cys Uncertain significance ★★ ⚠ same type
PDGFB p.Arg160Trp Uncertain significance ★★ ⚠ same type
PDGFB p.Arg187Gln Uncertain significance ★★ ⚠ same type
PDGFB p.Arg187Trp 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/pdgfb-p-arg129cys (accessed [today's date]).

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