Is FTCD p.Ile199= (c.597C>T) pathogenic?

FTCD p.Ile199= (c.597C>T) is classified Likely benign in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). Ultra-rare (popmax 0.033%, mid); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ile199= (c.597C>T)?

FTCD p.Ile199= (c.597C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ile199= (c.597C>T) in the general population?

FTCD p.Ile199= (c.597C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Ile199=

c.597C>T · rs773170658 · VCV2652808

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Conditions

formiminoglutamic aciduria

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 -3.7	GERP -2.4
Overall
CADD	3.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.00471% 76/1,612,998 alleles · ultra-rare exomes 72/1,460,626 · genomes 4/152,372 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
South Asian	0.0231%	4,338
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00381%	26,221
African / African-American	0.00266%	37,535
East Asian	0.00223%	44,872
Admixed American	0.00167%	60,028

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.Ile199=
Coding: c.597C>T
MANE Select: NM_206965
dbSNP: rs773170658
Type: single nucleotide variant
Location: chr21:46151597 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 199: the 'formiminotransferase c-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.Ile199Val Uncertain significance ★★ ⚠ same residue
FTCD p.Ile199Met Uncertain significance ★ ⚠ same residue
FTCD p.Arg255Ter Pathogenic ★★ same condition
FTCD p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Leu536Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala368Val 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/ftcd-p-ile199 (accessed [today's date]).

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