Is TFR2 p.Arg645= (c.1935C>T) pathogenic?

TFR2 p.Arg645= (c.1935C>T) is classified Likely benign in TFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). Absent from gnomAD v4.1; Associated with hereditary hemochromatosis.

What condition is associated with TFR2 p.Arg645= (c.1935C>T)?

TFR2 p.Arg645= (c.1935C>T) is associated with hereditary hemochromatosis (ClinVar).

How common is TFR2 p.Arg645= (c.1935C>T) in the general population?

TFR2 p.Arg645= (c.1935C>T) is absent from gnomAD v4.1 (gnomAD).

TFR2 p.Arg645=

c.1935C>T · rs2486117216 · VCV2985285

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary hemochromatosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	GERP 4.4, phastCons 1
Overall
CADD	11.62	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: TFR2
Protein: p.Arg645=
Coding: c.1935C>T
MANE Select: NM_003227
dbSNP: rs2486117216
Type: single nucleotide variant
Location: chr7:100627324 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.98

Full TFR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

TFR2 p.Arg645His Uncertain significance ★ ⚠ same residue
TFR2 p.Arg645Cys Uncertain significance ⚠ same residue
TFR2 c.1473+1G>A Likely pathogenic ★★ same condition
TFR2 c.1474-1G>A Likely pathogenic ★★ same condition
TFR2 c.1606-2A>G Pathogenic ★★ same condition
TFR2 c.1767+1G>T Likely pathogenic ★★ same condition
TFR2 c.286+1G>T Likely pathogenic ★★ same condition
TFR2 c.286+2T>C Likely pathogenic ★★ 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/tfr2-p-arg645 (accessed [today's date]).

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