Is FTCD p.Ala455Val (c.1364C>T) pathogenic?

FTCD p.Ala455Val (c.1364C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-17). AlphaMissense: likely benign (0.2074); Rare (popmax 0.164%, afr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Ala455Val (c.1364C>T)?

FTCD p.Ala455Val (c.1364C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Ala455Val (c.1364C>T) in the general population?

FTCD p.Ala455Val (c.1364C>T) is rare (popmax 0.164%, afr) (gnomAD).

What do computational predictors say about FTCD p.Ala455Val (c.1364C>T)?

AlphaMissense predicts likely benign (score 0.2074) — an in-silico prediction, not a clinical call.

FTCD p.Ala455Val

c.1364C>T · rs61735840 · VCV666112

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2074 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2074	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -9.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.2	GERP 1.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	21.4	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 0.164% African / African-American · 123/74,834 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.0209% 332/1,589,234 alleles · rare exomes 240/1,436,988 · genomes 92/152,246 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.188%	532
African / African-Americangrpmax	0.164%	608
South Asian	0.0246%	4,058
Remaining individualsnot grpmax-eligible	0.0194%	5,154
Middle Eastern	0.0177%	5,660
East Asian	0.0135%	7,411
Admixed American	0.0103%	9,669
European (non-Finnish)	0.00911%	10,980

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.Ala455Val
Coding: c.1364C>T
MANE Select: NM_206965
dbSNP: rs61735840
Type: single nucleotide variant
Location: chr21:46138587 (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.Ala455Thr 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-ala455val (accessed [today's date]).

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