Is GFPT1 p.Pro320= (c.960C>T) pathogenic?

GFPT1 p.Pro320= (c.960C>T) is classified Likely benign in GFPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Very rare (popmax 0.00833%, amr); Associated with congenital myasthenic syndrome 12.

What condition is associated with GFPT1 p.Pro320= (c.960C>T)?

GFPT1 p.Pro320= (c.960C>T) is associated with congenital myasthenic syndrome 12 (ClinVar).

How common is GFPT1 p.Pro320= (c.960C>T) in the general population?

GFPT1 p.Pro320= (c.960C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

GFPT1 p.Pro320=

c.960C>T · rs140814934 · VCV707336

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

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 0.7	GERP -3.7, phastCons 0.92
Overall
CADD	12.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,008 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00144% 21/1,461,384 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
European (non-Finnish)	0.00127%	78,639
South Asian	0.0011%	91,076

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.Pro320=
Coding: c.960C>T
MANE Select: NM_001244710
dbSNP: rs140814934
Type: single nucleotide variant
Location: chr2:69348220 (GRCh38)
Gene constraint: LOEUF 0.716 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 93.01 · 16 PDB
Residue 320: the 'isomerase' region

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-pro320 (accessed [today's date]).

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