Is PDGFRA p.Leu826Val (c.2476C>G) pathogenic?

PDGFRA p.Leu826Val (c.2476C>G) is classified Uncertain significance in PDGFRA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-13). AlphaMissense: likely benign (0.3016); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PDGFRA p.Leu826Val (c.2476C>G)?

PDGFRA p.Leu826Val (c.2476C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PDGFRA p.Leu826Val (c.2476C>G) in the general population?

PDGFRA p.Leu826Val (c.2476C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDGFRA p.Leu826Val (c.2476C>G)?

AlphaMissense predicts likely benign (score 0.3016) — an in-silico prediction, not a clinical call.

PDGFRA p.Leu826Val

c.2476C>G · VCV4861756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3016	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -3.25	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 1.8	GERP 1.2, phastCons 0.94
Regional constraint	o/e 0.31	constrained · MANE · 3,375 bp · p 9.7e-15 · regional, not allelic
Overall
CADD	23.9	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: PDGFRA
Protein: p.Leu826Val
Coding: c.2476C>G
MANE Select: NM_006206
Type: single nucleotide variant
Location: chr4:54285877 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 72.91 · 19 PDB
Residue 826: the protein kinase domain; a β-strand

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDGFRA c.1364+3A>G Uncertain significance ★★ same condition
PDGFRA c.1364+4T>C Uncertain significance ★★ same condition
PDGFRA c.1787-5C>G Uncertain significance ★★ same condition
PDGFRA c.2002+4G>A Uncertain significance ★★ same condition
PDGFRA c.2002+4G>T Uncertain significance ★★ same condition
PDGFRA c.2002+5G>C Uncertain significance ★★ same condition
PDGFRA c.2002+5G>T Uncertain significance ★★ same condition
PDGFRA c.2156+3G>C 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/pdgfra-p-leu826val (accessed [today's date]).

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