Is FTCD p.Arg477Trp (c.1429C>T) pathogenic?

FTCD p.Arg477Trp (c.1429C>T) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-07). AlphaMissense: likely benign (0.155); Ultra-rare (popmax 0.0261%, sas); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg477Trp (c.1429C>T)?

FTCD p.Arg477Trp (c.1429C>T) is associated with Inborn genetic diseases, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg477Trp (c.1429C>T) in the general population?

FTCD p.Arg477Trp (c.1429C>T) is ultra-rare (popmax 0.0261%, sas) (gnomAD).

What do computational predictors say about FTCD p.Arg477Trp (c.1429C>T)?

AlphaMissense predicts likely benign (score 0.155) — an in-silico prediction, not a clinical call.

FTCD p.Arg477Trp

c.1429C>T · rs556952105 · VCV1005867

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.155 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0261%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.155	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -12.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.86 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.4	GERP -0.83, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	26.8	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 0.0261% South Asian · 23/88,288 alleles

Filtering AF 0.0178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.015%

Overall 0.00612% 97/1,585,692 alleles · ultra-rare exomes 91/1,433,418 · genomes 6/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0261%	3,839
Finnishnot grpmax-eligible	0.0175%	5,700
Remaining individualsnot grpmax-eligible	0.0162%	6,159
European (non-Finnish)	0.00426%	23,460
Admixed American	0.00348%	28,714
African / African-American	0.00267%	37,410
East Asian	0.00226%	44,276

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.Arg477Trp
Coding: c.1429C>T
MANE Select: NM_206965
dbSNP: rs556952105
Type: single nucleotide variant
Location: chr21:46138522 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 477: 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.Arg477Gln 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-arg477trp (accessed [today's date]).

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