Is FTCD p.Ala140Pro (c.418G>C) pathogenic?

FTCD p.Ala140Pro (c.418G>C) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-29). AlphaMissense: ambiguous (0.3792); No allele count reported in gnomAD v4.1 (AN 1,572,446); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ala140Pro (c.418G>C)?

FTCD p.Ala140Pro (c.418G>C) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala140Pro (c.418G>C) in the general population?

FTCD p.Ala140Pro (c.418G>C) is no allele count reported in gnomAD v4.1 (AN 1,572,446) (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.Ala140Pro (c.418G>C)?

AlphaMissense predicts ambiguous (score 0.3792) — an in-silico prediction, not a clinical call.

FTCD p.Ala140Pro

c.418G>C · rs2079292124 · VCV2992522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3792 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,572,446)

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.3792	ambiguous
REVEL	0.528	indeterminate
SaProt	LLR -12.30	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	22.2	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

No allele count reported in gnomAD v4.1 (AN 1,572,446). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FTCD
Protein: p.Ala140Pro
Coding: c.418G>C
MANE Select: NM_206965
dbSNP: rs2079292124
Type: single nucleotide variant
Location: chr21:46151930 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 140: 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
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
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-ala140pro (accessed [today's date]).

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