Is FTCD p.Thr538= (c.1614C>T) pathogenic?

FTCD p.Thr538= (c.1614C>T) is classified Likely benign in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). Ultra-rare (popmax 0.05%, amr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Thr538= (c.1614C>T)?

FTCD p.Thr538= (c.1614C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Thr538= (c.1614C>T) in the general population?

FTCD p.Thr538= (c.1614C>T) is ultra-rare (popmax 0.05%, amr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Thr538=

c.1614C>T · rs138620208 · VCV1110836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, amr)

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.009	GERP -2.4, phastCons 0.54
Overall
CADD	0.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.05% Admixed American · 30/60,030 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.0145% 234/1,613,416 alleles · ultra-rare exomes 201/1,461,082 · genomes 33/152,334 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.05%	2,001
Middle Eastern	0.0495%	2,021
African / African-American	0.0213%	4,690
Remaining individualsnot grpmax-eligible	0.0192%	5,208
European (non-Finnish)	0.0147%	6,821

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.Thr538=
Coding: c.1614C>T
MANE Select: NM_206965
dbSNP: rs138620208
Type: single nucleotide variant
Location: chr21:46136999 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 538: the 'cyclodeaminase/cyclohydrolase' 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-thr538 (accessed [today's date]).

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