Is FTCD p.Arg299Trp (c.895C>T) pathogenic?

FTCD p.Arg299Trp (c.895C>T) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.196); Very rare (popmax 0.00374%, eas); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg299Trp (c.895C>T)?

FTCD p.Arg299Trp (c.895C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FTCD p.Arg299Trp (c.895C>T) in the general population?

FTCD p.Arg299Trp (c.895C>T) is very rare (popmax 0.00374%, eas) (gnomAD).

What do computational predictors say about FTCD p.Arg299Trp (c.895C>T)?

AlphaMissense predicts likely benign (score 0.196) — an in-silico prediction, not a clinical call.

FTCD p.Arg299Trp

c.895C>T · VCV4027204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00374%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.196	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 0.53, phastCons 0.98
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	25.5	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 0.00374% East Asian · 1/26,736 alleles

Filtering AF 3.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000285% 4/1,404,800 alleles · very rare exomes 3/1,259,114 · genomes 1/145,686 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00374%	26,736
Admixed American	0.00189%	53,050
European (non-Finnish)	0.000191%	524,882

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.Arg299Trp
Coding: c.895C>T
MANE Select: NM_206965
Type: single nucleotide variant
Location: chr21:46150130 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 299: a UniProt-annotated variant site (in figlu-uria; mild phenotype; decreased glutamate formimidoyltransferase activity; 57% wild-type activity); the 'formiminotransferase c-subdomain' 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.Arg299Pro 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-arg299trp (accessed [today's date]).

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