Is FTCD p.Ser12= (c.36G>A) pathogenic?

FTCD p.Ser12= (c.36G>A) is classified Benign in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). Rare (popmax 0.43%, afr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ser12= (c.36G>A)?

FTCD p.Ser12= (c.36G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ser12= (c.36G>A) in the general population?

FTCD p.Ser12= (c.36G>A) is rare (popmax 0.43%, afr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

FTCD p.Ser12=

c.36G>A · rs150970653 · VCV340451

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.43%, afr)

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -3.2
Overall
CADD	1.181	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.43% African / African-American · 323/75,058 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.377%

Overall 0.0336% 542/1,613,050 alleles · rare exomes 323/1,460,700 · genomes 219/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.43%	232
Admixed American	0.105%	953
Middle Eastern	0.0495%	2,019
Remaining individualsnot grpmax-eligible	0.048%	2,083
East Asian	0.0111%	8,977
South Asian	0.00988%	10,120
Finnishnot grpmax-eligible	0.00952%	10,502
European (non-Finnish)	0.00873%	11,456

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.Ser12=
Coding: c.36G>A
MANE Select: NM_206965
dbSNP: rs150970653
Type: single nucleotide variant
Location: chr21:46155488 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 12: 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.Ser12Leu Uncertain significance ★ ⚠ 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-ser12 (accessed [today's date]).

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