Is FTCD p.Asp89Gly (c.266A>G) pathogenic?

FTCD p.Asp89Gly (c.266A>G) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-02). AlphaMissense: likely pathogenic (0.9595); Very rare (popmax 0.00244%, eas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Asp89Gly (c.266A>G)?

FTCD p.Asp89Gly (c.266A>G) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Asp89Gly (c.266A>G) in the general population?

FTCD p.Asp89Gly (c.266A>G) is very rare (popmax 0.00244%, eas) (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.Asp89Gly (c.266A>G)?

AlphaMissense predicts likely pathogenic (score 0.9595) — an in-silico prediction, not a clinical call.

FTCD p.Asp89Gly

c.266A>G · rs896845617 · VCV2737009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.9595	likely pathogenic · top 3% in FTCD
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -11.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00244% East Asian · 1/40,988 alleles

Filtering AF 0.000395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000148%

Overall 0.000581% 9/1,550,054 alleles · very rare exomes 9/1,397,832 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00244%	40,988
South Asian	0.00238%	42,054
European (non-Finnish)	0.000523%	191,168

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.Asp89Gly
Coding: c.266A>G
MANE Select: NM_206965
dbSNP: rs896845617
Type: single nucleotide variant
Location: chr21:46153008 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 89: 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.Asp89= Benign/Likely benign ★★ 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-asp89gly (accessed [today's date]).

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