Is TFR2 p.Val583fs (c.1746del) pathogenic?

TFR2 p.Val583fs (c.1746del) is classified Pathogenic in TFR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-11). No gnomAD frequency available for this variant; Associated with hereditary hemochromatosis.

What condition is associated with TFR2 p.Val583fs (c.1746del)?

TFR2 p.Val583fs (c.1746del) is associated with hereditary hemochromatosis (ClinVar).

How common is TFR2 p.Val583fs (c.1746del) in the general population?

TFR2 p.Val583fs (c.1746del) is no gnomAD frequency available for this variant (gnomAD).

TFR2 p.Val583fs

c.1746del · rs1562838535 · VCV581375

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary hemochromatosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 3.3, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TFR2
Protein: p.Val583fs
Coding: c.1746del
MANE Select: NM_003227
dbSNP: rs1562838535
Type: Deletion
Location: chr7:100627598 (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.Val583= Likely benign ★ same residue
TFR2 c.33+1del Pathogenic/Likely pathogenic ★★ same condition
TFR2 p.Arg468fs Pathogenic/Likely pathogenic ★★ same condition
TFR2 p.Gln544fs Pathogenic/Likely pathogenic ★★ same condition
TFR2 p.Glu42fs Pathogenic/Likely pathogenic ★★ same condition
TFR2 p.Glu491fs Pathogenic/Likely pathogenic ★★ same condition
TFR2 p.Pro388fs Pathogenic/Likely pathogenic ★★ same condition
TFR2 c.458_473+6del 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-val583fs (accessed [today's date]).

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