Is FTCD p.Arg71Ter (c.211C>T) pathogenic?

FTCD p.Arg71Ter (c.211C>T) is classified Pathogenic/Likely pathogenic in FTCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0373%, afr); Associated with FTCD-related disorder.

What condition is associated with FTCD p.Arg71Ter (c.211C>T)?

FTCD p.Arg71Ter (c.211C>T) is associated with FTCD-related disorder, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg71Ter (c.211C>T) in the general population?

FTCD p.Arg71Ter (c.211C>T) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

FTCD p.Arg71Ter

c.211C>T · rs8133955 · VCV488890

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Conditions

FTCD-related disorder

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	predicted	premature termination codon in exon 2 of 14
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.27, phastCons 0.039
Overall
CADD	42.0	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 0.0373% African / African-American · 28/75,058 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00936% 151/1,612,840 alleles · ultra-rare exomes 120/1,460,498 · genomes 31/152,342 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0373%	2,681
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.00915%	10,926
South Asian	0.00769%	13,012
Admixed American	0.00333%	30,016

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.Arg71Ter
Coding: c.211C>T
MANE Select: NM_206965
dbSNP: rs8133955
Type: single nucleotide variant
Location: chr21:46154176 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 71: the 'formiminotransferase n-subdomain' region

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

Disease context

FTCD-related disorder

Also linked: formiminoglutamic aciduria

Similar variants

FTCD p.Arg71Pro Uncertain significance ★ ⚠ same residue
FTCD p.Arg255Ter 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
FTCD p.Ala455Thr 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-arg71ter (accessed [today's date]).

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