Is FTCD p.Arg333Ter (c.997C>T) pathogenic?

FTCD p.Arg333Ter (c.997C>T) is classified Likely pathogenic in FTCD (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-27). Very rare (popmax 0.00247%, sas); Associated with FTCD-related disorder.

What condition is associated with FTCD p.Arg333Ter (c.997C>T)?

FTCD p.Arg333Ter (c.997C>T) is associated with FTCD-related disorder (ClinVar).

How common is FTCD p.Arg333Ter (c.997C>T) in the general population?

FTCD p.Arg333Ter (c.997C>T) is very rare (popmax 0.00247%, sas) (gnomAD).

FTCD p.Arg333Ter

c.997C>T · rs1355632505 · VCV2632941

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00247%, sas)

Conditions

FTCD-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.4	GERP -2.3, phastCons 0.057
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00247% South Asian · 2/80,808 alleles

Filtering AF 0.000411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000154%

Overall 0.0004% 6/1,501,288 alleles · very rare exomes 3/1,352,784 · genomes 3/148,504 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00247%	40,404
European (non-Finnish)	0.000353%	283,035

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.Arg333Ter
Coding: c.997C>T
MANE Select: NM_206965
dbSNP: rs1355632505
Type: single nucleotide variant
Location: chr21:46145919 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 333: the 'linker' region

Full FTCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FTCD-related disorder

Similar variants

FTCD p.Arg333= Likely benign ★ same residue
FTCD p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Arg333fs Likely pathogenic ★ same residue
FTCD-AS1 n.71A>G Likely benign same condition
FTCD c.367+10C>G Likely benign same condition
FTCD c.*80C>G Likely benign same condition
FTCD p.Phe51= Likely benign same condition
FTCD p.Thr244= Likely benign 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-arg333ter (accessed [today's date]).

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