Is FTCD p.Glu508Lys (c.1522G>A) pathogenic?

FTCD p.Glu508Lys (c.1522G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-22). AlphaMissense: likely benign (0.0704); Very rare (popmax 0.00769%, sas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Glu508Lys (c.1522G>A)?

FTCD p.Glu508Lys (c.1522G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Glu508Lys (c.1522G>A) in the general population?

FTCD p.Glu508Lys (c.1522G>A) is very rare (popmax 0.00769%, sas) (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.Glu508Lys (c.1522G>A)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

FTCD p.Glu508Lys

c.1522G>A · rs376081092 · VCV2039791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -1.2
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	7.555	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,072 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00143% 23/1,613,034 alleles · very rare exomes 20/1,460,834 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,010
Remaining individualsnot grpmax-eligible	0.0048%	20,818
Admixed American	0.00333%	30,006
East Asian	0.00223%	44,876
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000763%	131,028

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.Glu508Lys
Coding: c.1522G>A
MANE Select: NM_206965
dbSNP: rs376081092
Type: single nucleotide variant
Location: chr21:46137256 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 508: 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.Glu508Ter Likely pathogenic ★ 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-glu508lys (accessed [today's date]).

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