Is TF p.Pro194= (c.582A>G) pathogenic?

TF p.Pro194= (c.582A>G) is classified Benign in TF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-31). Low-frequency (popmax 3.66%, afr); Associated with atransferrinemia.

What condition is associated with TF p.Pro194= (c.582A>G)?

TF p.Pro194= (c.582A>G) is associated with atransferrinemia (ClinVar).

How common is TF p.Pro194= (c.582A>G) in the general population?

TF p.Pro194= (c.582A>G) is low-frequency (popmax 3.66%, afr) (gnomAD).

How is Congenital atransferrinemia inherited?

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

TF p.Pro194=

c.582A>G · rs8177226 · VCV343434

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.66%, 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 -3.9	GERP -4.1
Overall
CADD	1.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.66% African / African-American · 2,748/75,062 alleles

Filtering AF 3.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.5%

Overall 0.198% 3,198/1,614,232 alleles · low-frequency exomes 1,627/1,461,894 · genomes 1,571/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.66%	27
Admixed American	0.283%	353
Remaining individualsnot grpmax-eligible	0.278%	359
Middle Eastern	0.198%	505
East Asian	0.02%	4,988
South Asian	0.0154%	6,506
European (non-Finnish)	0.00602%	16,620

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.Pro194=
Coding: c.582A>G
MANE Select: NM_001063
dbSNP: rs8177226
Type: single nucleotide variant
Location: chr3:133755442 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 194: 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-pro194 (accessed [today's date]).

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