Is FTCD p.Ala483Val (c.1448C>T) pathogenic?

FTCD p.Ala483Val (c.1448C>T) is classified Conflicting classifications of pathogenicity in FTCD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-08-10). AlphaMissense: likely pathogenic (0.6583); Ultra-rare (popmax 0.0513%, eas); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Ala483Val (c.1448C>T)?

FTCD p.Ala483Val (c.1448C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala483Val (c.1448C>T) in the general population?

FTCD p.Ala483Val (c.1448C>T) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

What do computational predictors say about FTCD p.Ala483Val (c.1448C>T)?

AlphaMissense predicts likely pathogenic (score 0.6583) — an in-silico prediction, not a clinical call.

FTCD p.Ala483Val

c.1448C>T · rs145609043 · VCV595818

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6583	likely pathogenic
REVEL	0.47	indeterminate
SaProt	LLR -12.85	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	29.6	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 0.0513% East Asian · 23/44,866 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0212% 342/1,612,432 alleles · ultra-rare exomes 312/1,460,114 · genomes 30/152,318 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.524%	191
East Asiangrpmax	0.0513%	1,951
Remaining individualsnot grpmax-eligible	0.0496%	2,015
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.01%	9,991
Admixed American	0.00833%	12,006
South Asian	0.00769%	13,008
African / African-American	0.00133%	75,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala483Val
Coding: c.1448C>T
MANE Select: NM_206965
dbSNP: rs145609043
Type: single nucleotide variant
Location: chr21:46137330 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 483: 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.Ala483= 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.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-ala483val (accessed [today's date]).

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