Is FTCD p.Val99fs (c.293dup) pathogenic?

FTCD p.Val99fs (c.293dup) is classified Pathogenic/Likely pathogenic in FTCD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-27). Very rare (popmax 0.000348%, nfe); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Val99fs (c.293dup)?

FTCD p.Val99fs (c.293dup) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Val99fs (c.293dup) in the general population?

FTCD p.Val99fs (c.293dup) is very rare (popmax 0.000348%, nfe) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Val99fs

c.293dup · rs1310075515 · VCV1071137

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000348%, nfe)

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 3 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.5	GERP -2.7
Overall
CADD	23.7	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 0.000348% European (non-Finnish) · 4/1,148,782 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000257% 4/1,553,766 alleles · very rare exomes 2/1,401,556 · genomes 2/152,210 · 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: FTCD
Protein: p.Val99fs
Coding: c.293dup
MANE Select: NM_206965
dbSNP: rs1310075515
Type: Duplication
Location: chr21:46152980 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 99: the 'formiminotransferase n-subdomain' 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.Val99Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
FTCD p.Pro331fs Pathogenic/Likely pathogenic ★★ same condition
FTCD c.1099-20dup Benign/Likely benign ★★ same condition
FTCD p.Arg341fs Likely pathogenic ★ same condition
FTCD p.Arg435fs Likely pathogenic ★ same condition
FTCD p.Glu205fs Pathogenic ★ same condition
FTCD p.Gly355fs Likely pathogenic ★ same condition
FTCD p.Ser100fs 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-val99fs (accessed [today's date]).

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