Is FTCD p.Arg142Gln (c.425G>A) pathogenic?

FTCD p.Arg142Gln (c.425G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.6918); Ultra-rare (popmax 0.0476%, sas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Arg142Gln (c.425G>A)?

FTCD p.Arg142Gln (c.425G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg142Gln (c.425G>A) in the general population?

FTCD p.Arg142Gln (c.425G>A) is ultra-rare (popmax 0.0476%, 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.Arg142Gln (c.425G>A)?

AlphaMissense predicts likely pathogenic (score 0.6918) — an in-silico prediction, not a clinical call.

FTCD p.Arg142Gln

c.425G>A · rs375990689 · VCV529458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6918 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0476%, sas)

Missense predictors

3/3 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	0.6918	likely pathogenic
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -13.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.4	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0476% South Asian · 41/86,190 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0319%

Overall 0.00528% 83/1,571,116 alleles · ultra-rare exomes 74/1,418,794 · genomes 9/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0476%	2,102
Admixed American	0.0093%	10,748
East Asian	0.00707%	14,139
Remaining individualsnot grpmax-eligible	0.00493%	20,279
Ashkenazi Jewishnot grpmax-eligible	0.00347%	28,834
African / African-American	0.0027%	37,032
European (non-Finnish)	0.00242%	41,384

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.Arg142Gln
Coding: c.425G>A
MANE Select: NM_206965
dbSNP: rs375990689
Type: single nucleotide variant
Location: chr21:46151923 (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-arg142gln (accessed [today's date]).

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