Is FTCD p.Pro331fs (c.990dup) pathogenic?

FTCD p.Pro331fs (c.990dup) is classified Pathogenic/Likely pathogenic in FTCD (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-01-24). Rare (popmax 0.567%, nfe); Associated with FTCD-related disorders.

What condition is associated with FTCD p.Pro331fs (c.990dup)?

FTCD p.Pro331fs (c.990dup) is associated with FTCD-related disorders, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Pro331fs (c.990dup) in the general population?

FTCD p.Pro331fs (c.990dup) is rare (popmax 0.567%, nfe) (gnomAD).

FTCD p.Pro331fs

c.990dup · rs398124234 · VCV4019

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.567%, nfe)

Conditions

FTCD-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.083	GERP -1.9
Overall
CADD	21.6	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 0.567% European (non-Finnish) · 6,424/1,132,996 alleles

Filtering AF 0.555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.551%

Overall 0.493% 7,421/1,504,188 alleles · rare exomes 6,866/1,354,976 · genomes 555/149,212 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.994%	101
European (non-Finnish)grpmax	0.567%	176
Remaining individualsnot grpmax-eligible	0.383%	261
South Asian	0.221%	453
Admixed American	0.151%	662
African / African-American	0.089%	1,123
Middle Eastern	0.0661%	1,512
Ashkenazi Jewishnot grpmax-eligible	0.0544%	1,837
East Asian	0.00268%	37,338

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro331fs
Coding: c.990dup
MANE Select: NM_206965
dbSNP: rs398124234
Type: Duplication
Location: chr21:46145925 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 331: the 'linker' region

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

Disease context

FTCD-related disorders

Also linked: formiminoglutamic aciduria

Similar variants

FTCD p.Val99fs Pathogenic/Likely pathogenic ★★ same condition
FTCD c.1099-20dup Benign/Likely benign ★★ same condition
FTCD p.Arg341fs Likely pathogenic ★ same condition
FTCD p.Arg435fs Likely pathogenic ★ same condition
FTCD p.Glu205fs Pathogenic ★ same condition
FTCD p.Gly355fs Likely pathogenic ★ same condition
FTCD p.Ser100fs Likely pathogenic ★ same condition
FTCD p.Tyr225fs Likely pathogenic ★ 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-pro331fs (accessed [today's date]).

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