Is TRMT1 p.Ser479fs (c.1435_1436del) pathogenic?

TRMT1 p.Ser479fs (c.14351436del) is classified Likely pathogenic in TRMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-16). Associated with intellectual developmental disorder, autosomal recessive 68.

What condition is associated with TRMT1 p.Ser479fs (c.1435_1436del)?

TRMT1 p.Ser479fs (c.1435_1436del) is associated with intellectual developmental disorder, autosomal recessive 68 (ClinVar).

TRMT1 p.Ser479fs

c.1435_1436del · VCV4795242

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual developmental disorder, autosomal recessive 68

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 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.88	GERP -1.6, phastCons 1

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

Variant & gene context

Gene: TRMT1
Protein: p.Ser479fs
Coding: c.1435_1436del
MANE Select: NM_001136035
Type: Microsatellite
Location: chr19:13107821 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 1 PDB
Residue 479: the trm1 methyltransferase domain

Full TRMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder, autosomal recessive 68 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRMT1 p.Cys387fs Likely pathogenic ★ same condition
TRMT1 p.Arg512Ter Likely pathogenic ★★ same condition
TRMT1 p.Gln219fs Pathogenic ★★ same condition
TRMT1 p.Lys130fs Likely pathogenic ★★ same condition
TRMT1 p.Tyr445fs Pathogenic ★★ same condition
TRMT1 p.Arg195Trp Uncertain significance ★★ ⚠ same condition
TRMT1 p.Gly352Arg Uncertain significance ★★ ⚠ same condition
TRMT1 p.Gly360Ser 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/trmt1-p-ser479fs (accessed [today's date]).

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