Is FTCD p.Arg84Cys (c.250C>T) pathogenic?

FTCD p.Arg84Cys (c.250C>T) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: ambiguous (0.5356); Ultra-rare (popmax 0.0294%, amr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Arg84Cys (c.250C>T)?

FTCD p.Arg84Cys (c.250C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg84Cys (c.250C>T) in the general population?

FTCD p.Arg84Cys (c.250C>T) is ultra-rare (popmax 0.0294%, amr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

What do computational predictors say about FTCD p.Arg84Cys (c.250C>T)?

AlphaMissense predicts ambiguous (score 0.5356) — an in-silico prediction, not a clinical call.

FTCD p.Arg84Cys

c.250C>T · rs576603499 · VCV2200279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.5356	ambiguous
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -13.83	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 0.25, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0294% Admixed American · 15/51,010 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00497% 77/1,549,044 alleles · ultra-rare exomes 63/1,396,702 · genomes 14/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0294%	3,401
South Asian	0.0214%	4,669
Remaining individualsnot grpmax-eligible	0.00833%	12,007
European (non-Finnish)	0.00331%	30,178
African / African-American	0.00137%	73,204

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.Arg84Cys
Coding: c.250C>T
MANE Select: NM_206965
dbSNP: rs576603499
Type: single nucleotide variant
Location: chr21:46153024 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 84: 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.Arg84His Uncertain significance ★ ⚠ same residue
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

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-arg84cys (accessed [today's date]).

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