Is PDGFRB p.Ser591Phe (c.1772C>T) pathogenic?

PDGFRB p.Ser591Phe (c.1772C>T) is classified Uncertain significance in PDGFRB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.2997); Absent from gnomAD v4.1.

How common is PDGFRB p.Ser591Phe (c.1772C>T) in the general population?

PDGFRB p.Ser591Phe (c.1772C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRB p.Ser591Phe (c.1772C>T)?

AlphaMissense predicts likely benign (score 0.2997) — an in-silico prediction, not a clinical call.

PDGFRB p.Ser591Phe

c.1772C>T · VCV4079516

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2997	likely benign
REVEL	0.617	indeterminate
SaProt	LLR -11.19	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.12, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 16 kb · p 5.4e-12 · regional, not allelic
Overall
CADD	25.0	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

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.Ser591Phe
Coding: c.1772C>T
MANE Select: NM_002609
Type: single nucleotide variant
Location: chr5:150125480 (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

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-ser591phe (accessed [today's date]).

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