Is TF p.His369= (c.1107C>T) pathogenic?

TF p.His369= (c.1107C>T) is classified Conflicting classifications of pathogenicity in TF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.0893%, afr); Associated with atransferrinemia.

What condition is associated with TF p.His369= (c.1107C>T)?

TF p.His369= (c.1107C>T) is associated with atransferrinemia (ClinVar).

How common is TF p.His369= (c.1107C>T) in the general population?

TF p.His369= (c.1107C>T) is ultra-rare (popmax 0.0893%, afr) (gnomAD).

How is Congenital atransferrinemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TF p.His369=

c.1107C>T · rs112157819 · VCV343442

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0893%, afr)

Conditions

atransferrinemia

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 -20	GERP -3.5
Overall
CADD	0.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0893% African / African-American · 67/75,006 alleles

Filtering AF 0.0721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0659%

Overall 0.00762% 123/1,614,030 alleles · ultra-rare exomes 71/1,461,822 · genomes 52/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0893%	1,119
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0144%	6,945
Admixed American	0.00666%	15,006
South Asian	0.00659%	15,179
European (non-Finnish)	0.00288%	34,705

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: TF
Protein: p.His369=
Coding: c.1107C>T
MANE Select: NM_001063
dbSNP: rs112157819
Type: single nucleotide variant
Location: chr3:133759233 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 369: an α-helix; the transferrin-like 2 domain

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

Disease context

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

For Congenital atransferrinemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

TF c.-18C>T Uncertain significance ★★ same condition
TF p.Ala72Val Uncertain significance ★★ ⚠ same condition
TF p.Gln264Glu Uncertain significance ★★ ⚠ same condition
TF p.Ile229Thr Uncertain significance ★★ ⚠ same condition
TF p.Thr112Ala Uncertain significance ★★ ⚠ same condition
TF p.Val451Ala Uncertain significance ★★ ⚠ same condition
TF c.1688-4C>A Benign/Likely benign ★★ same condition
TF c.216+14G>C Benign/Likely benign ★★ 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/tf-p-his369 (accessed [today's date]).

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