Is TET2 p.Pro616= (c.1848A>C) pathogenic?

TET2 p.Pro616= (c.1848A>C) is classified Likely benign in TET2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-01). Absent from gnomAD v4.1.

How common is TET2 p.Pro616= (c.1848A>C) in the general population?

TET2 p.Pro616= (c.1848A>C) is absent from gnomAD v4.1 (gnomAD).

TET2 p.Pro616=

c.1848A>C · VCV3388791

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.48	GERP -3.8
Overall
CADD	0.736	PHRED · no single calibrated threshold — expert panels disagree

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.Pro616=
Coding: c.1848A>C
MANE Select: NM_001127208
Type: single nucleotide variant
Location: chr4:105235790 (GRCh38)
Gene constraint: LOEUF 1.997 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.31 · 6 PDB

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

Similar variants

TET2 p.Pro616Arg Uncertain significance ★ ⚠ same residue
TET2 p.Pro616Leu Uncertain significance ★ ⚠ same residue
TET2 p.Pro616Ser Uncertain significance ★ ⚠ same residue
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

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-pro616 (accessed [today's date]).

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