Is FTCD p.Thr50Ile (c.149C>T) pathogenic?

FTCD p.Thr50Ile (c.149C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-28). AlphaMissense: likely pathogenic (0.9488); Ultra-rare (popmax 0.0826%, afr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Thr50Ile (c.149C>T)?

FTCD p.Thr50Ile (c.149C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Thr50Ile (c.149C>T) in the general population?

FTCD p.Thr50Ile (c.149C>T) is ultra-rare (popmax 0.0826%, afr) (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.Thr50Ile (c.149C>T)?

AlphaMissense predicts likely pathogenic (score 0.9488) — an in-silico prediction, not a clinical call.

FTCD p.Thr50Ile

c.149C>T · rs199769706 · VCV1407255

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9488 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.9488	likely pathogenic · top 4% in FTCD
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0826% African / African-American · 62/75,062 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.00453% 73/1,612,804 alleles · ultra-rare exomes 37/1,460,438 · genomes 36/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0826%	1,211
Admixed American	0.0117%	8,575
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,888
European (non-Finnish)	8.47e-05%	1,179,966

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.Thr50Ile
Coding: c.149C>T
MANE Select: NM_206965
dbSNP: rs199769706
Type: single nucleotide variant
Location: chr21:46154238 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 50: 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.Arg255Ter Pathogenic ★★ same condition
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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
FTCD p.Ala455Thr 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-thr50ile (accessed [today's date]).

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