Is TF p.Leu247= (c.739C>T) pathogenic?

TF p.Leu247= (c.739C>T) is classified Benign in TF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 22.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with atransferrinemia.

What condition is associated with TF p.Leu247= (c.739C>T)?

TF p.Leu247= (c.739C>T) is associated with atransferrinemia (ClinVar).

How is Congenital atransferrinemia inherited?

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

TF p.Leu247=

Q: How common is TF p.Leu247= (c.739C>T) in the general population?

TF p.Leu247= (c.739C>T) is common (popmax 22.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.739C>T · rs1799852 · VCV343439

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 22.7%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.98	GERP -4.3
Overall
CADD	8.538	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.7% East Asian · 10,208/44,874 alleles

Filtering AF 22.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.2%

Overall 10.9% 175,443/1,614,108 alleles · common exomes 159,010/1,461,874 · genomes 16,433/152,234 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	22.7%	4
Finnishnot grpmax-eligible	16.7%	6
South Asian	14.8%	7
Middle Eastern	13.9%	7
Admixed American	13.3%	8
Ashkenazi Jewishnot grpmax-eligible	12.2%	8
Remaining individualsnot grpmax-eligible	11.9%	8
European (non-Finnish)	9.87%	10
Amishnot grpmax-eligible	8.33%	12
African / African-American	6.16%	16

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.Leu247=
Coding: c.739C>T
MANE Select: NM_001063
dbSNP: rs1799852
Type: single nucleotide variant
Location: chr3:133756878 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 247: a turn; the transferrin-like 1 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-leu247 (accessed [today's date]).

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