Is FTCD p.Tyr124Ter (c.372C>G) pathogenic?

FTCD p.Tyr124Ter (c.372C>G) is classified Pathogenic/Likely pathogenic in FTCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-05). Very rare (popmax 0.00189%, amr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Tyr124Ter (c.372C>G)?

FTCD p.Tyr124Ter (c.372C>G) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Tyr124Ter (c.372C>G) in the general population?

FTCD p.Tyr124Ter (c.372C>G) is very rare (popmax 0.00189%, amr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FTCD p.Tyr124Ter

c.372C>G · rs777286639 · VCV2800589

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00189%, amr)

Conditions

formiminoglutamic aciduria

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.20	gain · loss 0.18 · independent
Constraint at this position
Conservation	phyloP 2.8	GERP -0.92, phastCons 1
Overall
CADD	43.0	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 0.00189% Admixed American · 1/52,872 alleles

Overall 6.39e-05% 1/1,564,498 alleles · very rare exomes 1/1,412,164 · genomes 0/152,334 · 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.Tyr124Ter
Coding: c.372C>G
MANE Select: NM_206965
dbSNP: rs777286639
Type: single nucleotide variant
Location: chr21:46151976 (GRCh38)

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

Disease context

formiminoglutamic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

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-tyr124ter (accessed [today's date]).

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