Is FTCD p.Ala368Val (c.1103C>T) pathogenic?

FTCD p.Ala368Val (c.1103C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-15). AlphaMissense: likely benign (0.1575); Very rare (popmax 0.00986%, eas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ala368Val (c.1103C>T)?

FTCD p.Ala368Val (c.1103C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala368Val (c.1103C>T) in the general population?

FTCD p.Ala368Val (c.1103C>T) is very rare (popmax 0.00986%, eas) (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.Ala368Val (c.1103C>T)?

AlphaMissense predicts likely benign (score 0.1575) — an in-silico prediction, not a clinical call.

FTCD p.Ala368Val

c.1103C>T · rs1033001525 · VCV1678565

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00986%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.1575	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -11.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	21.7	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 0.00986% East Asian · 4/40,554 alleles

Filtering AF 0.0033% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00124% 19/1,537,778 alleles · very rare exomes 18/1,386,088 · genomes 1/151,690 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00986%	10,139
European (non-Finnish)	0.00123%	81,490
South Asian	0.00119%	83,724

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.Ala368Val
Coding: c.1103C>T
MANE Select: NM_206965
dbSNP: rs1033001525
Type: single nucleotide variant
Location: chr21:46145574 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 368: the 'cyclodeaminase/cyclohydrolase' 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
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.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Val 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-ala368val (accessed [today's date]).

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