Is FTCD p.Arg84His (c.251G>A) pathogenic?

FTCD p.Arg84His (c.251G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-01). AlphaMissense: likely pathogenic (0.6953); Ultra-rare (popmax 0.0118%, amr); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Arg84His (c.251G>A)?

FTCD p.Arg84His (c.251G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg84His (c.251G>A) in the general population?

FTCD p.Arg84His (c.251G>A) is ultra-rare (popmax 0.0118%, amr) (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.Arg84His (c.251G>A)?

AlphaMissense predicts likely pathogenic (score 0.6953) — an in-silico prediction, not a clinical call.

FTCD p.Arg84His

c.251G>A · rs748347001 · VCV1449953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6953 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

Computational evidence

Protein change
AlphaMissense	0.6953	likely pathogenic
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	33.0	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 0.0118% Admixed American · 6/50,998 alleles

Filtering AF 0.00512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00347%

Overall 0.00123% 19/1,549,048 alleles · ultra-rare exomes 17/1,396,720 · genomes 2/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0118%	8,500
East Asian	0.00733%	13,639
Remaining individualsnot grpmax-eligible	0.00167%	60,042
African / African-American	0.00137%	73,192
South Asian	0.00119%	84,042
European (non-Finnish)	0.00061%	163,821

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.Arg84His
Coding: c.251G>A
MANE Select: NM_206965
dbSNP: rs748347001
Type: single nucleotide variant
Location: chr21:46153023 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 84: the 'formiminotransferase n-subdomain' region

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

Similar variants

FTCD p.Arg84Cys Uncertain significance ★ ⚠ same residue
FTCD p.Arg255Ter Pathogenic ★★ same condition
FTCD p.Arg71Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Leu536Ter Pathogenic/Likely pathogenic ★★ same condition
FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala368Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala418Thr Uncertain significance ★★ ⚠ 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-arg84his (accessed [today's date]).

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