Is FTCD p.Arg333fs (c.998_1002del) pathogenic?

FTCD p.Arg333fs (c.9981002del) is classified Likely pathogenic in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Arg333fs (c.998_1002del)?

FTCD p.Arg333fs (c.998_1002del) is associated with formiminoglutamic aciduria (ClinVar).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Arg333fs

c.998_1002del · VCV3587714

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

formiminoglutamic aciduria

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 9 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -1.9, phastCons 1

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

Variant & gene context

Gene: FTCD
Protein: p.Arg333fs
Coding: c.998_1002del
MANE Select: NM_206965
Type: Deletion
Location: chr21:46145914 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 333: the 'linker' region

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

Disease context

formiminoglutamic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

FTCD p.Arg333= Likely benign ★ same residue
FTCD p.Ala62fs Likely pathogenic ★★ same condition
FTCD p.Val344fs Pathogenic/Likely pathogenic ★★ same condition
FTCD c.1068_1098+24del Likely pathogenic ★ same condition
FTCD c.1443+1del Likely pathogenic ★ same condition
FTCD p.Ala361fs Likely pathogenic ★ same condition
FTCD p.Arg333Ter Likely pathogenic ★ same residue
FTCD p.Glu332fs Likely 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/ftcd-p-arg333fs (accessed [today's date]).

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