Is TRNT1 p.Phe52Ser (c.155T>C) pathogenic?

TRNT1 p.Phe52Ser (c.155T>C) is classified Uncertain significance in TRNT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). AlphaMissense: likely pathogenic (0.9342); Very rare (popmax 0.000257%, nfe); Associated with congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome.

How common is TRNT1 p.Phe52Ser (c.155T>C) in the general population?

TRNT1 p.Phe52Ser (c.155T>C) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about TRNT1 p.Phe52Ser (c.155T>C)?

AlphaMissense predicts likely pathogenic (score 0.9342) — an in-silico prediction, not a clinical call.

TRNT1 p.Phe52Ser

Q: What condition is associated with TRNT1 p.Phe52Ser (c.155T>C)?

TRNT1 p.Phe52Ser (c.155T>C) 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.155T>C · rs1705383984 · VCV1010033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9342	likely pathogenic
REVEL	0.731	pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 19 kb · p 1e-08 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000257% European (non-Finnish) · 3/1,165,122 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00019% 3/1,578,244 alleles · very rare exomes 3/1,425,904 · genomes 0/152,340 · 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.Phe52Ser
Coding: c.155T>C
MANE Select: NM_182916
dbSNP: rs1705383984
Type: single nucleotide variant
Location: chr3:3137266 (GRCh38)
Gene constraint: LOEUF 1.232 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.00 · 3 PDB
Residue 52: 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.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
TRNT1 p.Ala358Gly 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-phe52ser (accessed [today's date]).

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