Is FTCD p.Arg320Gln (c.959G>A) pathogenic?

FTCD p.Arg320Gln (c.959G>A) is classified Uncertain significance in FTCD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1617); Ultra-rare (popmax 0.0998%, mid); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg320Gln (c.959G>A)?

FTCD p.Arg320Gln (c.959G>A) is associated with Inborn genetic diseases, myoepithelial tumor, formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg320Gln (c.959G>A) in the general population?

FTCD p.Arg320Gln (c.959G>A) is ultra-rare (popmax 0.0998%, mid) (gnomAD).

What do computational predictors say about FTCD p.Arg320Gln (c.959G>A)?

AlphaMissense predicts likely benign (score 0.1617) — an in-silico prediction, not a clinical call.

FTCD p.Arg320Gln

c.959G>A · rs77740289 · VCV665224

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1617 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0998%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1617	likely benign
REVEL	0.697	pathogenic-leaning
SaProt	LLR -9.26	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	30.0	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 0.0998% Middle Eastern · 6/6,014 alleles

Filtering AF 0.0434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0241% 385/1,600,810 alleles · ultra-rare exomes 339/1,448,542 · genomes 46/152,268 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0998%	1,002
African / African-American	0.0348%	2,874
European (non-Finnish)	0.0277%	3,608
Remaining individualsnot grpmax-eligible	0.0161%	6,197
Finnishnot grpmax-eligible	0.0113%	8,876
South Asian	0.0112%	8,943
Admixed American	0.00169%	59,304

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.Arg320Gln
Coding: c.959G>A
MANE Select: NM_206965
dbSNP: rs77740289
Type: single nucleotide variant
Location: chr21:46146275 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 320: the 'formiminotransferase c-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: myoepithelial tumor formiminoglutamic aciduria

Similar variants

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
FTCD p.Ala368Val 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-arg320gln (accessed [today's date]).

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