Is TRNT1 p.Phe80fs (c.240del) pathogenic?

TRNT1 p.Phe80fs (c.240del) is classified Pathogenic in TRNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-07). Very rare (popmax 8.47e-05%, nfe); Associated with congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome.

How common is TRNT1 p.Phe80fs (c.240del) in the general population?

TRNT1 p.Phe80fs (c.240del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

TRNT1 p.Phe80fs

Q: What condition is associated with TRNT1 p.Phe80fs (c.240del)?

TRNT1 p.Phe80fs (c.240del) 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.240del · rs1297648080 · VCV1074723

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.2e-05% 1/1,613,922 alleles · very rare exomes 0/1,461,744 · genomes 1/152,178 · 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: TRNT1
Protein: p.Phe80fs
Coding: c.240del
MANE Select: NM_182916
dbSNP: rs1297648080
Type: Deletion
Location: chr3:3137348 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 80: a β-strand

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 c.1055_1056+5del Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.His108fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Leu125fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Phe167fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Ser289fs Pathogenic ★★ same condition
TRNT1 p.Thr337fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Val181fs Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Asn178fs 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-phe80fs (accessed [today's date]).

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