Is FTCD p.Ala464= (c.1392C>G) pathogenic?

FTCD p.Ala464= (c.1392C>G) is classified Benign in FTCD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ala464= (c.1392C>G)?

FTCD p.Ala464= (c.1392C>G) is associated with formiminoglutamic aciduria (ClinVar).

How is Formiminoglutamic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FTCD p.Ala464=

Q: How common is FTCD p.Ala464= (c.1392C>G) in the general population?

FTCD p.Ala464= (c.1392C>G) is common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1392C>G · rs1047179 · VCV95424

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 65.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.246	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.7
Overall
CADD	0.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 65.4% Admixed American · 37,269/56,962 alleles

Filtering AF 64.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.6%

Overall 47.5% 751,893/1,583,174 alleles · common exomes 676,236/1,431,192 · genomes 75,657/151,982 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	65.4%	2
African / African-American	52.6%	2
Amishnot grpmax-eligible	52%	2
Ashkenazi Jewishnot grpmax-eligible	50.3%	2
Remaining individualsnot grpmax-eligible	48.4%	2
European (non-Finnish)	47.7%	2
Middle Eastern	45.3%	2
East Asian	40.1%	2
Finnishnot grpmax-eligible	39.9%	3
South Asian	35.5%	3

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.Ala464=
Coding: c.1392C>G
MANE Select: NM_206965
dbSNP: rs1047179
Type: single nucleotide variant
Location: chr21:46138559 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 464: 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.Ala464Val Conflicting classifications of pathogenicity ★ 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.Ala368Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala418Thr 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-ala464 (accessed [today's date]).

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