Is FTCD p.Arg255Ter (c.763C>T) pathogenic?

FTCD p.Arg255Ter (c.763C>T) is classified Pathogenic in FTCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-14). Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg255Ter (c.763C>T)?

FTCD p.Arg255Ter (c.763C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg255Ter (c.763C>T) in the general population?

FTCD p.Arg255Ter (c.763C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

FTCD p.Arg255Ter

c.763C>T · rs140217223 · VCV632385

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

Inborn genetic diseases

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	predicted	premature termination codon in exon 6 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -0.64, phastCons 1
Overall
CADD	50.0	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 0.012% African / African-American · 9/74,900 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00508% 82/1,612,738 alleles · ultra-rare exomes 76/1,460,560 · genomes 6/152,178 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,322
European (non-Finnish)	0.00593%	16,856
Remaining individualsnot grpmax-eligible	0.0032%	31,232
East Asian	0.00223%	44,888

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.Arg255Ter
Coding: c.763C>T
MANE Select: NM_206965
dbSNP: rs140217223
Type: single nucleotide variant
Location: chr21:46150399 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 255: the 'formiminotransferase c-subdomain' region

Full FTCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: formiminoglutamic aciduria

Similar variants

FTCD p.Arg255Gln Uncertain significance ★ ⚠ same residue
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.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val 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-arg255ter (accessed [today's date]).

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