Is TRNT1 p.Ile245fs (c.733dup) pathogenic?

TRNT1 p.Ile245fs (c.733dup) is classified Pathogenic in TRNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-22). Absent from gnomAD; Associated with congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome.

How common is TRNT1 p.Ile245fs (c.733dup) in the general population?

TRNT1 p.Ile245fs (c.733dup) is absent from gnomAD (gnomAD).

TRNT1 p.Ile245fs

Q: What condition is associated with TRNT1 p.Ile245fs (c.733dup)?

TRNT1 p.Ile245fs (c.733dup) is associated with congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (ClinVar).

Q: How is Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome inherited?

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

c.733dup · rs1706032688 · VCV959702

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP -0.38, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRNT1
Protein: p.Ile245fs
Coding: c.733dup
MANE Select: NM_182916
dbSNP: rs1706032688
Type: Duplication
Location: chr3:3146547 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 245: a UniProt-annotated variant site (in sifd; uncertain significance); an α-helix

Full TRNT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TRNT1 p.Glu403fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 c.482-3dup Likely benign ★★ same condition
TRNT1 p.Ala148fs Pathogenic ★ same condition
TRNT1 p.Asn171fs Pathogenic ★ same condition
TRNT1 p.Asn284fs Pathogenic ★ same condition
TRNT1 p.Asp168Ter Pathogenic ★ same condition
TRNT1 p.Asp348fs Pathogenic ★ same condition
TRNT1 p.Gln414fs Pathogenic ★ 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/trnt1-p-ile245fs (accessed [today's date]).

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