Is FTCD p.Ala364Glu (c.1091C>A) pathogenic?

FTCD p.Ala364Glu (c.1091C>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.8991); Ultra-rare (popmax 0.0529%, afr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Ala364Glu (c.1091C>A)?

FTCD p.Ala364Glu (c.1091C>A) is associated with Inborn genetic diseases (ClinVar).

How common is FTCD p.Ala364Glu (c.1091C>A) in the general population?

FTCD p.Ala364Glu (c.1091C>A) is ultra-rare (popmax 0.0529%, afr) (gnomAD).

What do computational predictors say about FTCD p.Ala364Glu (c.1091C>A)?

AlphaMissense predicts likely pathogenic (score 0.8991) — an in-silico prediction, not a clinical call.

FTCD p.Ala364Glu

c.1091C>A · VCV4027196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0529%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8991	likely pathogenic · top 8% in FTCD
REVEL	0.221	benign-leaning
SaProt	LLR -15.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -0.76, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	23.1	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 0.0529% African / African-American · 7/13,230 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0176%

Overall 0.00212% 14/659,060 alleles · ultra-rare exomes 11/656,742 · genomes 3/2,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0529%	1,890
South Asian	0.00417%	23,996
European (non-Finnish)	0.00104%	96,440

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.Ala364Glu
Coding: c.1091C>A
MANE Select: NM_206965
Type: single nucleotide variant
Location: chr21:46145825 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 364: 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

Similar variants

FTCD p.Ala364Gly Uncertain significance ★ ⚠ same residue
FTCD p.Arg255Ter 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
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-ala364glu (accessed [today's date]).

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