Is FTCD p.Thr389Arg (c.1166C>G) pathogenic?

FTCD p.Thr389Arg (c.1166C>G) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0871); Ultra-rare (popmax 0.0116%, amr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Thr389Arg (c.1166C>G)?

FTCD p.Thr389Arg (c.1166C>G) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Thr389Arg (c.1166C>G) in the general population?

FTCD p.Thr389Arg (c.1166C>G) is ultra-rare (popmax 0.0116%, amr) (gnomAD).

What do computational predictors say about FTCD p.Thr389Arg (c.1166C>G)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

FTCD p.Thr389Arg

c.1166C>G · rs545214029 · VCV340424

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -7.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.33, phastCons 0.15
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	17.42	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0116% Admixed American · 6/51,532 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00344%

Overall 0.00103% 16/1,550,822 alleles · ultra-rare exomes 14/1,398,664 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0116%	8,589
South Asian	0.00356%	28,067
East Asian	0.00244%	40,948
Remaining individualsnot grpmax-eligible	0.00166%	60,140
European (non-Finnish)	0.000436%	229,503

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.Thr389Arg
Coding: c.1166C>G
MANE Select: NM_206965
dbSNP: rs545214029
Type: single nucleotide variant
Location: chr21:46145511 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 389: 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.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
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-thr389arg (accessed [today's date]).

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