Is FTCD p.Ala22Thr (c.64G>A) pathogenic?

FTCD p.Ala22Thr (c.64G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.0938); Ultra-rare (popmax 0.02%, mid); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Ala22Thr (c.64G>A)?

FTCD p.Ala22Thr (c.64G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala22Thr (c.64G>A) in the general population?

FTCD p.Ala22Thr (c.64G>A) is ultra-rare (popmax 0.02%, 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.Ala22Thr (c.64G>A)?

AlphaMissense predicts likely benign (score 0.0938) — an in-silico prediction, not a clinical call.

FTCD p.Ala22Thr

c.64G>A · rs769270784 · VCV2139974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0938 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.0938	likely benign
REVEL	0.58	indeterminate
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	24.6	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 0.02% Middle Eastern · 1/4,998 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000745% 12/1,609,892 alleles · ultra-rare exomes 11/1,457,694 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.02%	4,998
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,550
African / African-American	0.00134%	74,822
European (non-Finnish)	0.000763%	131,040

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.Ala22Thr
Coding: c.64G>A
MANE Select: NM_206965
dbSNP: rs769270784
Type: single nucleotide variant
Location: chr21:46154323 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 22: 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.Arg255Ter Pathogenic ★★ same condition
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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
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-ala22thr (accessed [today's date]).

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