Is AGRN p.Ala933Val (c.2798C>T) pathogenic?

AGRN p.Ala933Val (c.2798C>T) is classified Conflicting classifications of pathogenicity in AGRN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-20). Very rare (popmax 0.00424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGRN p.Ala933Val (c.2798C>T)?

AGRN p.Ala933Val (c.2798C>T) is associated with Inborn genetic diseases, congenital myasthenic syndrome 8 (ClinVar).

How common is AGRN p.Ala933Val (c.2798C>T) in the general population?

AGRN p.Ala933Val (c.2798C>T) is very rare (popmax 0.00424%, nfe) (gnomAD).

AGRN p.Ala933Val

c.2798C>T · rs375711798 · VCV654059

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00424%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.061	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP 0.47, phastCons 0.23
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	13.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00424% European (non-Finnish) · 50/1,180,012 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00294%

Overall 0.00328% 53/1,613,930 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00424%	23,600
African / African-American	0.00267%	37,475
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ala933Val
Coding: c.2798C>T
MANE Select: NM_198576
dbSNP: rs375711798
Type: single nucleotide variant
Location: chr1:1046081 (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 933: the kazal-like 9 domain; a disulfide bond

Full AGRN 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: congenital myasthenic syndrome 8

Similar variants

AGRN p.Ala933Thr Uncertain significance ★ same residue
AGRN p.Ala933= 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

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-ala933val (accessed [today's date]).

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