Is GFPT1 p.Pro223= (c.669T>C) pathogenic?

GFPT1 p.Pro223= (c.669T>C) is classified Likely benign in GFPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-16). Very rare (popmax 0.00137%, nfe); Associated with congenital myasthenic syndrome 12.

What condition is associated with GFPT1 p.Pro223= (c.669T>C)?

GFPT1 p.Pro223= (c.669T>C) is associated with congenital myasthenic syndrome 12 (ClinVar).

How common is GFPT1 p.Pro223= (c.669T>C) in the general population?

GFPT1 p.Pro223= (c.669T>C) is very rare (popmax 0.00137%, nfe) (gnomAD).

GFPT1 p.Pro223=

c.669T>C · rs903308197 · VCV1606992

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00137%, nfe)

Conditions

congenital myasthenic syndrome 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.2
Overall
CADD	1.578	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00137% European (non-Finnish) · 16/1,164,194 alleles

Filtering AF 0.000814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000658%

Overall 0.00111% 16/1,444,338 alleles · very rare

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: GFPT1
Protein: p.Pro223=
Coding: c.669T>C
MANE Select: NM_001244710
dbSNP: rs903308197
Type: single nucleotide variant
Location: chr2:69354505 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 93.01 · 16 PDB
Residue 223: the glutamine amidotransferase type-2 domain; a β-strand

Full GFPT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GFPT1 c.408+5G>A Likely pathogenic ★★ same condition
GFPT1 c.686-2A>G Pathogenic ★★ same condition
GFPT1 p.Arg111Cys Pathogenic/Likely pathogenic ★★ same condition
GFPT1 p.Arg111His Pathogenic/Likely pathogenic ★★ same condition
GFPT1 p.Arg563Ter Pathogenic/Likely pathogenic ★★ same condition
GFPT1 p.Thr15Met Pathogenic ★★ ⚠ same condition
GFPT1 c.1324+3G>A Uncertain significance ★★ same condition
GFPT1 c.1597+5A>G 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/gfpt1-p-pro223 (accessed [today's date]).

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