Is FTCD p.Thr174Met (c.521C>T) pathogenic?

FTCD p.Thr174Met (c.521C>T) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: likely benign (0.2441); Very rare (popmax 0.00534%, afr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Thr174Met (c.521C>T)?

FTCD p.Thr174Met (c.521C>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Thr174Met (c.521C>T) in the general population?

FTCD p.Thr174Met (c.521C>T) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Formiminoglutamic aciduria inherited?

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

What do computational predictors say about FTCD p.Thr174Met (c.521C>T)?

AlphaMissense predicts likely benign (score 0.2441) — an in-silico prediction, not a clinical call.

FTCD p.Thr174Met

c.521C>T · rs757064013 · VCV962891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2441 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.2441	likely benign
REVEL	0.829	moderately pathogenic-leaning
SaProt	LLR -13.19	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	27.1	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 0.00534% African / African-American · 4/74,946 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,612,890 alleles · very rare exomes 24/1,460,632 · genomes 2/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,736
Finnishnot grpmax-eligible	0.00318%	31,473
European (non-Finnish)	0.00161%	62,102
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Thr174Met
Coding: c.521C>T
MANE Select: NM_206965
dbSNP: rs757064013
Type: single nucleotide variant
Location: chr21:46151673 (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-thr174met (accessed [today's date]).

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