Is FTCD p.Leu536Ter (c.1607T>A) pathogenic?

FTCD p.Leu536Ter (c.1607T>A) is classified Pathogenic/Likely pathogenic in FTCD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-22). Rare (popmax 0.381%, afr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Leu536Ter (c.1607T>A)?

FTCD p.Leu536Ter (c.1607T>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Leu536Ter (c.1607T>A) in the general population?

FTCD p.Leu536Ter (c.1607T>A) is rare (popmax 0.381%, afr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Leu536Ter

c.1607T>A · rs149266909 · VCV194395

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.381%, afr)

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.2, phastCons 1
Overall
CADD	41.0	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 0.381% African / African-American · 286/75,034 alleles

Filtering AF 0.345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.0192% 310/1,613,420 alleles · rare exomes 142/1,461,130 · genomes 168/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.381%	262
Admixed American	0.0183%	5,457
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.000508%	196,659

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.Leu536Ter
Coding: c.1607T>A
MANE Select: NM_206965
dbSNP: rs149266909
Type: single nucleotide variant
Location: chr21:46137006 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 536: 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.Leu536= Likely benign ★ same residue
FTCD p.Arg255Ter Pathogenic ★★ same condition
FTCD p.Arg71Ter 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-leu536ter (accessed [today's date]).

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