Is FTCD p.Asp412Asn (c.1234G>A) pathogenic?

FTCD p.Asp412Asn (c.1234G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely pathogenic (0.6507); Very rare (popmax 0.00942%, amr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Asp412Asn (c.1234G>A)?

FTCD p.Asp412Asn (c.1234G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Asp412Asn (c.1234G>A) in the general population?

FTCD p.Asp412Asn (c.1234G>A) is very rare (popmax 0.00942%, amr) (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.Asp412Asn (c.1234G>A)?

AlphaMissense predicts likely pathogenic (score 0.6507) — an in-silico prediction, not a clinical call.

FTCD p.Asp412Asn

c.1234G>A · rs751878966 · VCV3013863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6507 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00942%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.6507	likely pathogenic
REVEL	0.731	pathogenic-leaning
SaProt	LLR -15.11	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	26.7	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 0.00942% Admixed American · 5/53,090 alleles

Filtering AF 0.0037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.000578% 9/1,557,040 alleles · very rare exomes 8/1,404,900 · genomes 1/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00942%	10,618
South Asian	0.00118%	84,552
European (non-Finnish)	0.000261%	383,773

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.Asp412Asn
Coding: c.1234G>A
MANE Select: NM_206965
dbSNP: rs751878966
Type: single nucleotide variant
Location: chr21:46145443 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 412: the 'cyclodeaminase/cyclohydrolase' region; an active site

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
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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-asp412asn (accessed [today's date]).

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