Is TRNT1 p.Phe349= (c.1047C>T) pathogenic?

TRNT1 p.Phe349= (c.1047C>T) is classified Likely benign in TRNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). Very rare (popmax 0.00993%, sas); Associated with congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome.

How common is TRNT1 p.Phe349= (c.1047C>T) in the general population?

TRNT1 p.Phe349= (c.1047C>T) is very rare (popmax 0.00993%, sas) (gnomAD).

TRNT1 p.Phe349=

Q: What condition is associated with TRNT1 p.Phe349= (c.1047C>T)?

TRNT1 p.Phe349= (c.1047C>T) 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.1047C>T · rs62228638 · VCV1940380

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00993%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.18, phastCons 1
Overall
CADD	8.284	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00993% South Asian · 9/90,658 alleles

Filtering AF 0.00516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.000745% 12/1,610,812 alleles · very rare exomes 11/1,458,732 · genomes 1/152,080 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00993%	10,073
Admixed American	0.00168%	59,578
European (non-Finnish)	0.00017%	589,209

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.Phe349=
Coding: c.1047C>T
MANE Select: NM_182916
dbSNP: rs62228638
Type: single nucleotide variant
Location: chr3:3147694 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 349: 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.Phe349Val Uncertain significance ★ ⚠ same residue
TRNT1 p.Arg190Ile Pathogenic ★★ same condition
TRNT1 p.Arg412Ter Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Glu277Ter Pathogenic/Likely pathogenic ★★ same condition
TRNT1 p.Ile223Thr Pathogenic ★★ same condition
TRNT1 p.Lys416Glu Pathogenic/Likely pathogenic ★★ ⚠ same condition
TRNT1 p.Ala273Gly Uncertain significance ★★ ⚠ same condition
TRNT1 p.Ala316Thr Uncertain significance ★★ ⚠ 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-phe349 (accessed [today's date]).

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