Is TFR2 p.Pro393= (c.1179C>T) pathogenic?

TFR2 p.Pro393= (c.1179C>T) is classified Likely benign in TFR2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-05). Rare (popmax 0.109%, eas); Associated with hereditary hemochromatosis.

What condition is associated with TFR2 p.Pro393= (c.1179C>T)?

TFR2 p.Pro393= (c.1179C>T) is associated with hereditary hemochromatosis, hemochromatosis type 3 (ClinVar).

How common is TFR2 p.Pro393= (c.1179C>T) in the general population?

TFR2 p.Pro393= (c.1179C>T) is rare (popmax 0.109%, eas) (gnomAD).

TFR2 p.Pro393=

c.1179C>T · rs149590949 · VCV700889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

Conditions

hereditary hemochromatosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.9	GERP -8.2
Overall
CADD	0.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,834 alleles

Filtering AF 0.0849% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.0149% 240/1,611,778 alleles · rare exomes 222/1,459,504 · genomes 18/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	915
African / African-American	0.016%	6,249
Remaining individualsnot grpmax-eligible	0.0144%	6,927
European (non-Finnish)	0.0136%	7,371
South Asian	0.00991%	10,093
Admixed American	0.00167%	59,804

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: TFR2
Protein: p.Pro393=
Coding: c.1179C>T
MANE Select: NM_003227
dbSNP: rs149590949
Type: single nucleotide variant
Location: chr7:100630980 (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

Also linked: hemochromatosis type 3

Similar variants

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.1606-8A>G Likely 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
TFR2 c.287-2A>G 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-pro393 (accessed [today's date]).

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