Is FTCD p.Gln513fs (c.1537dup) pathogenic?

FTCD p.Gln513fs (c.1537dup) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). Very rare (popmax 0.00446%, eas).

How common is FTCD p.Gln513fs (c.1537dup) in the general population?

FTCD p.Gln513fs (c.1537dup) is very rare (popmax 0.00446%, eas) (gnomAD).

FTCD p.Gln513fs

c.1537dup · rs779856936 · VCV2573553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (13 of 14, 1 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP 1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,846 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000124% 2/1,610,332 alleles · very rare exomes 2/1,458,032 · genomes 0/152,300 · joint denominator

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.Gln513fs
Coding: c.1537dup
MANE Select: NM_206965
dbSNP: rs779856936
Type: Duplication
Location: chr21:46137240 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 513: the 'cyclodeaminase/cyclohydrolase' region

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

Similar variants

FTCD p.Pro331fs Pathogenic/Likely pathogenic ★★ same type
FTCD p.Val99fs Pathogenic/Likely pathogenic ★★ same type
FTCD c.1099-20dup Benign/Likely benign ★★ same type
FTCD p.Arg341fs Likely pathogenic ★ same type
FTCD p.Arg435fs Likely pathogenic ★ same type
FTCD p.Glu205fs Pathogenic ★ same type
FTCD p.Gly355fs Likely pathogenic ★ same type
FTCD p.Ser100fs Likely pathogenic ★ same type

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-gln513fs (accessed [today's date]).

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