Is TF p.Ser208= (c.624G>A) pathogenic?

TF p.Ser208= (c.624G>A) is classified Benign in TF (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 47%, eas) — too common for a highly-penetrant pathogenic allele; Associated with atransferrinemia.

What condition is associated with TF p.Ser208= (c.624G>A)?

TF p.Ser208= (c.624G>A) 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.Ser208=

Q: How common is TF p.Ser208= (c.624G>A) in the general population?

TF p.Ser208= (c.624G>A) is common (popmax 47%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.624G>A · rs12769 · VCV343436

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 47%, 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 -7.3	GERP -4.1
Overall
CADD	0.867	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47% East Asian · 21,067/44,866 alleles

Filtering AF 46.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.2%

Overall 31.9% 514,041/1,613,820 alleles · common exomes 472,839/1,461,658 · genomes 41,202/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	47%	2
Admixed American	41.7%	2
South Asian	40.5%	2
European (non-Finnish)	31.8%	3
Amishnot grpmax-eligible	31.5%	3
Finnishnot grpmax-eligible	30.3%	3
Remaining individualsnot grpmax-eligible	30.3%	3
Ashkenazi Jewishnot grpmax-eligible	23.9%	4
Middle Eastern	19%	5
African / African-American	12.4%	8

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.Ser208=
Coding: c.624G>A
MANE Select: NM_001063
dbSNP: rs12769
Type: single nucleotide variant
Location: chr3:133755484 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.39 · 69 PDB
Residue 208: 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-ser208 (accessed [today's date]).

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