Is FTCD p.Ala455Thr (c.1363G>A) pathogenic?

FTCD p.Ala455Thr (c.1363G>A) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-25). AlphaMissense: likely benign (0.1752); Ultra-rare (popmax 0.0122%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Ala455Thr (c.1363G>A)?

FTCD p.Ala455Thr (c.1363G>A) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala455Thr (c.1363G>A) in the general population?

FTCD p.Ala455Thr (c.1363G>A) is ultra-rare (popmax 0.0122%, nfe) (gnomAD).

What do computational predictors say about FTCD p.Ala455Thr (c.1363G>A)?

AlphaMissense predicts likely benign (score 0.1752) — an in-silico prediction, not a clinical call.

FTCD p.Ala455Thr

c.1363G>A · rs376572763 · VCV1355344

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1752	likely benign
REVEL	0.505	indeterminate
SaProt	LLR -9.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	24.1	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 0.0122% European (non-Finnish) · 143/1,175,318 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00985%

Overall 0.00937% 149/1,590,022 alleles · ultra-rare exomes 143/1,437,854 · genomes 6/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0122%	8,219
Remaining individualsnot grpmax-eligible	0.00485%	20,621
Finnishnot grpmax-eligible	0.00199%	50,256
African / African-American	0.00134%	74,754
South Asian	0.00112%	89,370

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.Ala455Thr
Coding: c.1363G>A
MANE Select: NM_206965
dbSNP: rs376572763
Type: single nucleotide variant
Location: chr21:46138588 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 455: the 'cyclodeaminase/cyclohydrolase' region

Full FTCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: formiminoglutamic aciduria

Similar variants

FTCD p.Ala455Val Uncertain significance ★★ ⚠ 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.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val 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-ala455thr (accessed [today's date]).

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