Is PDGFB p.Ala92Ser (c.274G>T) pathogenic?

PDGFB p.Ala92Ser (c.274G>T) is classified Uncertain significance in PDGFB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: ambiguous (0.4673); Absent from gnomAD v4.1.

How common is PDGFB p.Ala92Ser (c.274G>T) in the general population?

PDGFB p.Ala92Ser (c.274G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFB p.Ala92Ser (c.274G>T)?

AlphaMissense predicts ambiguous (score 0.4673) — an in-silico prediction, not a clinical call.

PDGFB p.Ala92Ser

c.274G>T · rs2517762224 · VCV2785932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4673 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4673	ambiguous
REVEL	0.621	indeterminate
SaProt	LLR -10.02	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 18 kb · p 0.021 · regional, not allelic
Overall
CADD	24.0	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: PDGFB
Protein: p.Ala92Ser
Coding: c.274G>T
MANE Select: NM_002608
dbSNP: rs2517762224
Type: single nucleotide variant
Location: chr22:39231804 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 73.77 · 6 PDB
Residue 92: an α-helix

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

Similar variants

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
PDGFB p.Arg207Gln 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-ala92ser (accessed [today's date]).

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