Is AGRN p.Pro1938= (c.5814C>T) pathogenic?

AGRN p.Pro1938= (c.5814C>T) is classified Benign/Likely benign in AGRN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-17). Rare (popmax 0.858%, sas); Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Pro1938= (c.5814C>T)?

AGRN p.Pro1938= (c.5814C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Pro1938= (c.5814C>T) in the general population?

AGRN p.Pro1938= (c.5814C>T) is rare (popmax 0.858%, sas) (gnomAD).

AGRN p.Pro1938=

c.5814C>T · rs369308183 · VCV474160

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.858%, sas)

Conditions

congenital myasthenic syndrome 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.129	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -2.5
Overall
CADD	1.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.858% South Asian · 770/89,738 alleles

Filtering AF 0.808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.788%

Overall 0.0697% 1,120/1,606,230 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.858%	117
Middle Eastern	0.11%	913
Remaining individualsnot grpmax-eligible	0.0659%	1,517
Admixed American	0.0355%	2,815
Finnishnot grpmax-eligible	0.024%	4,172
European (non-Finnish)	0.0226%	4,426
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,440

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: AGRN
Protein: p.Pro1938=
Coding: c.5814C>T
MANE Select: NM_198576
dbSNP: rs369308183
Type: single nucleotide variant
Location: chr1:1053915 (GRCh38)
Gene constraint: LOEUF 0.73 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.79 · 1 PDB
Residue 1938: the laminin g-like 3 domain

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

Disease context

congenital myasthenic syndrome 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGRN p.Pro1938Leu Likely benign same residue
AGRN c.3632-1G>C Likely pathogenic ★★ same condition
AGRN p.Arg1671Ter Pathogenic/Likely pathogenic ★★ same condition
AGRN p.Arg834Ter Pathogenic/Likely pathogenic ★★ same condition
AGRN p.Gly1582Arg Pathogenic ★★ same condition
AGRN p.Gly1675Ser Pathogenic/Likely pathogenic ★★ same condition
AGRN c.1177+4A>G Uncertain significance ★★ same condition
AGRN c.1384+6C>T 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/agrn-p-pro1938 (accessed [today's date]).

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