Is TET2 p.Pro480Ser (c.1438C>T) pathogenic?

TET2 p.Pro480Ser (c.1438C>T) is classified Uncertain significance in TET2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0875); Absent from gnomAD v4.1; Associated with plasma cell myeloma.

What condition is associated with TET2 p.Pro480Ser (c.1438C>T)?

TET2 p.Pro480Ser (c.1438C>T) is associated with plasma cell myeloma (ClinVar).

How common is TET2 p.Pro480Ser (c.1438C>T) in the general population?

TET2 p.Pro480Ser (c.1438C>T) is absent from gnomAD v4.1 (gnomAD).

How is Multiple myeloma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TET2 p.Pro480Ser (c.1438C>T)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

TET2 p.Pro480Ser

c.1438C>T · rs1578673280 · VCV800332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

plasma cell myeloma

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.91, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 43 kb · p 0.41 · regional, not allelic
Overall
CADD	13.76	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: TET2
Protein: p.Pro480Ser
Coding: c.1438C>T
MANE Select: NM_001127208
dbSNP: rs1578673280
Type: single nucleotide variant
Location: chr4:105235380 (GRCh38)
Gene constraint: LOEUF 1.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.31 · 6 PDB
Residue 480: the 'disordered' region

Full TET2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

plasma cell myeloma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple myeloma (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

TET2 p.Arg544Ter Pathogenic/Likely pathogenic ★★ same type
TET2 p.Gln622Ter Pathogenic/Likely pathogenic ★★ same type
TET2 c.3409+42G>T Uncertain significance ★★ same type
TET2 p.Ala1072Pro Uncertain significance ★★ ⚠ same type
TET2 p.Ala1158Val Uncertain significance ★★ same type
TET2 p.Ala1769Pro Uncertain significance ★★ ⚠ same type
TET2 p.Arg1095Lys Uncertain significance ★★ ⚠ same type
TET2 p.Arg1134Thr 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/tet2-p-pro480ser (accessed [today's date]).

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