Is FTCD p.Arg517Cys (c.1549C>T) pathogenic?

FTCD p.Arg517Cys (c.1549C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-27). AlphaMissense: likely benign (0.1046); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg517Cys (c.1549C>T)?

FTCD p.Arg517Cys (c.1549C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg517Cys (c.1549C>T) in the general population?

FTCD p.Arg517Cys (c.1549C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about FTCD p.Arg517Cys (c.1549C>T)?

AlphaMissense predicts likely benign (score 0.1046) — an in-silico prediction, not a clinical call.

FTCD p.Arg517Cys

c.1549C>T · rs1188352065 · VCV1400411

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1046	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -11.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.31	acceptor gain · deltas
Pangolin	Δ0.42	gain · loss 0.37 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.5	GERP 0.097, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	26.5	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00254% 41/1,613,694 alleles · ultra-rare exomes 40/1,461,468 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00314%	31,892
South Asian	0.0011%	91,088

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.Arg517Cys
Coding: c.1549C>T
MANE Select: NM_206965
dbSNP: rs1188352065
Type: single nucleotide variant
Location: chr21:46137064 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 517: the 'cyclodeaminase/cyclohydrolase' 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.Arg517His 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.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val 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-arg517cys (accessed [today's date]).

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