Is TET3 p.Pro501= (c.1503G>A) pathogenic?

TET3 p.Pro501= (c.1503G>A) is classified Likely benign in TET3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-06). Very rare (popmax 0.00893%, eas); Associated with TET3-related disorder.

What condition is associated with TET3 p.Pro501= (c.1503G>A)?

TET3 p.Pro501= (c.1503G>A) is associated with TET3-related disorder (ClinVar).

How common is TET3 p.Pro501= (c.1503G>A) in the general population?

TET3 p.Pro501= (c.1503G>A) is very rare (popmax 0.00893%, eas) (gnomAD).

TET3 p.Pro501=

c.1503G>A · rs781550128 · VCV3030240

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Conditions

TET3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.6	GERP -4.1
Overall
CADD	0.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,810 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00155% 25/1,612,282 alleles · very rare exomes 22/1,460,348 · genomes 3/151,934 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,202
Admixed American	0.00334%	29,967
South Asian	0.0022%	45,495
Remaining individualsnot grpmax-eligible	0.0016%	62,448
African / African-American	0.00133%	74,908
European (non-Finnish)	0.00127%	78,635

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TET3
Protein: p.Pro501=
Coding: c.1503G>A
MANE Select: NM_001287491
dbSNP: rs781550128
Type: single nucleotide variant
Location: chr2:74047420 (GRCh38)
Gene constraint: LOEUF 0.213 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.49 · 2 PDB
Residue 501: the 'disordered' region

Full TET3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TET3-related disorder

Similar variants

TET3 p.Pro501Leu Uncertain significance ★ ⚠ same residue
TET3 p.Arg1744His Uncertain significance ★★ ⚠ same condition
TET3 p.Arg430Gly Uncertain significance ★★ ⚠ same condition
TET3 p.Thr59Ala Uncertain significance ★★ ⚠ same condition
TET3 c.3130-5C>T Uncertain significance ★ same condition
TET3 p.Ala263= Uncertain significance ★ same condition
TET3 p.Ala502Thr Uncertain significance ★ ⚠ same condition
TET3 p.Ala511Val 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/tet3-p-pro501 (accessed [today's date]).

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