Is TF p.Asn595= (c.1785C>T) pathogenic?

TF p.Asn595= (c.1785C>T) is classified Conflicting classifications of pathogenicity in TF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-05-27). Very rare (popmax 0.00407%, nfe); Associated with atransferrinemia.

What condition is associated with TF p.Asn595= (c.1785C>T)?

TF p.Asn595= (c.1785C>T) is associated with atransferrinemia (ClinVar).

How common is TF p.Asn595= (c.1785C>T) in the general population?

TF p.Asn595= (c.1785C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

How is Congenital atransferrinemia inherited?

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

TF p.Asn595=

c.1785C>T · rs757985238 · VCV343449

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

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 -5.7	GERP -4.1
Overall
CADD	0.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,180,034 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00297% 48/1,614,082 alleles · very rare exomes 47/1,461,884 · genomes 1/152,198 · joint denominator

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.Asn595=
Coding: c.1785C>T
MANE Select: NM_001063
dbSNP: rs757985238
Type: single nucleotide variant
Location: chr3:133775530 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 595: 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-asn595 (accessed [today's date]).

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