Is FTCD p.Glu147Lys (c.439G>A) pathogenic?

FTCD p.Glu147Lys (c.439G>A) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-03). AlphaMissense: ambiguous (0.4308); Ultra-rare (popmax 0.0357%, mid); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Glu147Lys (c.439G>A)?

FTCD p.Glu147Lys (c.439G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Glu147Lys (c.439G>A) in the general population?

FTCD p.Glu147Lys (c.439G>A) is ultra-rare (popmax 0.0357%, mid) (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.Glu147Lys (c.439G>A)?

AlphaMissense predicts ambiguous (score 0.4308) — an in-silico prediction, not a clinical call.

FTCD p.Glu147Lys

c.439G>A · rs754659947 · VCV459968

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4308 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.4308	ambiguous
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -10.07	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.24	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	29.9	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 0.0357% Middle Eastern · 2/5,606 alleles

Filtering AF 0.0232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.02%

Overall 0.0103% 161/1,564,516 alleles · ultra-rare exomes 156/1,412,304 · genomes 5/152,212 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0357%	2,803
South Asian	0.0327%	3,058
European (non-Finnish)	0.0106%	9,469
Remaining individualsnot grpmax-eligible	0.00661%	15,137
East Asian	0.00476%	21,019
African / African-American	0.00271%	36,881
Admixed American	0.0019%	52,720

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.Glu147Lys
Coding: c.439G>A
MANE Select: NM_206965
dbSNP: rs754659947
Type: single nucleotide variant
Location: chr21:46151909 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 147: 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.Glu147Gln 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-glu147lys (accessed [today's date]).

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