Is FTCD p.Met489Leu (c.1465A>T) pathogenic?

FTCD p.Met489Leu (c.1465A>T) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). AlphaMissense: likely benign (0.119); Absent from gnomAD v4.1; Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Met489Leu (c.1465A>T)?

FTCD p.Met489Leu (c.1465A>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Met489Leu (c.1465A>T) in the general population?

FTCD p.Met489Leu (c.1465A>T) is absent from gnomAD v4.1 (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.Met489Leu (c.1465A>T)?

AlphaMissense predicts likely benign (score 0.119) — an in-silico prediction, not a clinical call.

FTCD p.Met489Leu

c.1465A>T · rs757551172 · VCV1957014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.119 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.119	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	17.74	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FTCD
Protein: p.Met489Leu
Coding: c.1465A>T
MANE Select: NM_206965
dbSNP: rs757551172
Type: single nucleotide variant
Location: chr21:46137313 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 489: 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

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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-met489leu (accessed [today's date]).

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