Is FTCD p.Pro139= (c.417G>A) pathogenic?

FTCD p.Pro139= (c.417G>A) is classified Benign in FTCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-29). Common (popmax 17.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Pro139= (c.417G>A)?

FTCD p.Pro139= (c.417G>A) 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.Pro139=

Q: How common is FTCD p.Pro139= (c.417G>A) in the general population?

FTCD p.Pro139= (c.417G>A) is common (popmax 17.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.417G>A · rs61729391 · VCV95426

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 17.4%, sas) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.4
Overall
CADD	0.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.4% South Asian · 15,034/86,252 alleles

Filtering AF 17.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.1%

Overall 8.81% 138,530/1,571,930 alleles · common exomes 126,712/1,419,662 · genomes 11,818/152,268 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	17.4%	6
Amishnot grpmax-eligible	11.1%	9
Finnishnot grpmax-eligible	10.6%	9
Middle Eastern	9.9%	10
Remaining individualsnot grpmax-eligible	8.76%	11
European (non-Finnish)	8.6%	12
East Asian	7.31%	14
African / African-American	6.13%	16
Ashkenazi Jewishnot grpmax-eligible	5.88%	17
Admixed American	4.02%	25

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.Pro139=
Coding: c.417G>A
MANE Select: NM_206965
dbSNP: rs61729391
Type: single nucleotide variant
Location: chr21:46151931 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 139: 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-pro139 (accessed [today's date]).

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