Is FTCD p.Ile20= (c.60C>T) pathogenic?

FTCD p.Ile20= (c.60C>T) is classified Likely benign in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Ultra-rare (popmax 0.0411%, mid); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ile20= (c.60C>T)?

FTCD p.Ile20= (c.60C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ile20= (c.60C>T) in the general population?

FTCD p.Ile20= (c.60C>T) is ultra-rare (popmax 0.0411%, mid) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Ile20=

c.60C>T · rs374622555 · VCV2040164

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, mid)

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -5.9	GERP -2.8
Overall
CADD	9.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0411% Middle Eastern · 2/4,862 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.00292% 47/1,609,450 alleles · ultra-rare exomes 41/1,457,168 · genomes 6/152,282 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0411%	2,431
African / African-American	0.00534%	18,735
Admixed American	0.00502%	19,929
European (non-Finnish)	0.00305%	32,753
East Asian	0.00223%	44,792
Remaining individualsnot grpmax-eligible	0.00161%	62,222

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.Ile20=
Coding: c.60C>T
MANE Select: NM_206965
dbSNP: rs374622555
Type: single nucleotide variant
Location: chr21:46154327 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 20: 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.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
FTCD p.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr 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-ile20 (accessed [today's date]).

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