Is FTCD p.Asp157Tyr (c.469G>T) pathogenic?

FTCD p.Asp157Tyr (c.469G>T) is classified Likely benign in FTCD (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.1448); Rare (popmax 0.714%, sas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Asp157Tyr (c.469G>T)?

FTCD p.Asp157Tyr (c.469G>T) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Asp157Tyr (c.469G>T) in the general population?

FTCD p.Asp157Tyr (c.469G>T) is rare (popmax 0.714%, sas) (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.Asp157Tyr (c.469G>T)?

AlphaMissense predicts likely benign (score 0.1448) — an in-silico prediction, not a clinical call.

FTCD p.Asp157Tyr

c.469G>T · rs532226691 · VCV780197

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1448 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.714%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

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	0.1448	likely benign
REVEL	0.363	indeterminate
SaProt	LLR -11.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.1	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	22.3	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 0.714% South Asian · 650/91,080 alleles

Filtering AF 0.668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.65%

Overall 0.0427% 688/1,612,874 alleles · rare exomes 643/1,460,498 · genomes 45/152,376 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.714%	140
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Middle Eastern	0.0166%	6,042
Admixed American	0.00167%	60,028
European (non-Finnish)	0.00119%	84,284

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.Asp157Tyr
Coding: c.469G>T
MANE Select: NM_206965
dbSNP: rs532226691
Type: single nucleotide variant
Location: chr21:46151725 (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-asp157tyr (accessed [today's date]).

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