Is FTCD p.Cys107Arg (c.319T>C) pathogenic?

FTCD p.Cys107Arg (c.319T>C) is classified Conflicting classifications of pathogenicity in FTCD (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-04-24). AlphaMissense: likely pathogenic (0.7564); Ultra-rare (popmax 0.065%, amr); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Cys107Arg (c.319T>C)?

FTCD p.Cys107Arg (c.319T>C) is associated with Inborn genetic diseases, intellectual disability, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Cys107Arg (c.319T>C) in the general population?

FTCD p.Cys107Arg (c.319T>C) is ultra-rare (popmax 0.065%, amr) (gnomAD).

What do computational predictors say about FTCD p.Cys107Arg (c.319T>C)?

AlphaMissense predicts likely pathogenic (score 0.7564) — an in-silico prediction, not a clinical call.

FTCD p.Cys107Arg

c.319T>C · rs377359525 · VCV665719

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7564 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7564	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	26.0	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 0.065% Admixed American · 34/52,296 alleles

Filtering AF 0.0556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0481% 752/1,562,668 alleles · ultra-rare exomes 703/1,410,342 · genomes 49/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.065%	1,538
European (non-Finnish)	0.0594%	1,684
Remaining individualsnot grpmax-eligible	0.0429%	2,331
African / African-American	0.00405%	24,707
South Asian	0.00353%	28,335
Finnishnot grpmax-eligible	0.0017%	58,820

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.Cys107Arg
Coding: c.319T>C
MANE Select: NM_206965
dbSNP: rs377359525
Type: single nucleotide variant
Location: chr21:46152955 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 107: the 'formiminotransferase n-subdomain' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability formiminoglutamic aciduria

Similar variants

FTCD p.Cys107= Likely benign ★ 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.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val 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-cys107arg (accessed [today's date]).

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