Is TF p.Ser144= (c.432C>T) pathogenic?

TF p.Ser144= (c.432C>T) is classified Benign in TF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). Low-frequency (popmax 3.5%, afr); Associated with atransferrinemia.

What condition is associated with TF p.Ser144= (c.432C>T)?

TF p.Ser144= (c.432C>T) is associated with atransferrinemia (ClinVar).

How common is TF p.Ser144= (c.432C>T) in the general population?

TF p.Ser144= (c.432C>T) is low-frequency (popmax 3.5%, afr) (gnomAD).

How is Congenital atransferrinemia inherited?

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

TF p.Ser144=

c.432C>T · rs41298987 · VCV343432

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.5%, 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 -15	GERP -4.3
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.5% African / African-American · 2,629/75,034 alleles

Filtering AF 3.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.35%

Overall 0.195% 3,149/1,614,178 alleles · low-frequency exomes 1,652/1,461,886 · genomes 1,497/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.5%	29
Remaining individualsnot grpmax-eligible	0.274%	366
Admixed American	0.253%	395
Middle Eastern	0.215%	466
East Asian	0.029%	3,452
South Asian	0.0176%	5,693
European (non-Finnish)	0.0131%	7,613

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.Ser144=
Coding: c.432C>T
MANE Select: NM_001063
dbSNP: rs41298987
Type: single nucleotide variant
Location: chr3:133754601 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 144: the transferrin-like 1 domain; an α-helix

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-ser144 (accessed [today's date]).

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