Is FTCD p.His515fs (c.1543del) pathogenic?

FTCD p.His515fs (c.1543del) is classified Likely pathogenic in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-30). Very rare (popmax 0.000424%, nfe); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.His515fs (c.1543del)?

FTCD p.His515fs (c.1543del) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.His515fs (c.1543del) in the general population?

FTCD p.His515fs (c.1543del) is very rare (popmax 0.000424%, nfe) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.His515fs

c.1543del · VCV3587700

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, 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	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 · substitutions only
Constraint at this position
Conservation	phyloP -16	GERP -2.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,994 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,676 alleles · very rare exomes 5/1,461,446 · genomes 0/152,230 · 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.His515fs
Coding: c.1543del
MANE Select: NM_206965
Type: Deletion
Location: chr21:46137070 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 515: 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.His515= Likely benign ★ same residue
FTCD p.Ala62fs Likely pathogenic ★★ same condition
FTCD p.Val344fs Pathogenic/Likely pathogenic ★★ same condition
FTCD c.1068_1098+24del Likely pathogenic ★ same condition
FTCD c.1443+1del Likely pathogenic ★ same condition
FTCD p.Ala361fs Likely pathogenic ★ same condition
FTCD p.Arg333fs Likely pathogenic ★ same condition
FTCD p.Glu332fs 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-his515fs (accessed [today's date]).

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