Is AGRN p.Phe1690= (c.5070C>T) pathogenic?

AGRN p.Phe1690= (c.5070C>T) is classified Benign in AGRN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital myasthenic syndrome 8.

What condition is associated with AGRN p.Phe1690= (c.5070C>T)?

AGRN p.Phe1690= (c.5070C>T) is associated with congenital myasthenic syndrome 8 (ClinVar).

AGRN p.Phe1690=

Q: How common is AGRN p.Phe1690= (c.5070C>T) in the general population?

AGRN p.Phe1690= (c.5070C>T) is common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5070C>T · rs17160776 · VCV128313

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 13.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

congenital myasthenic syndrome 8

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 -11	GERP -3
Overall
CADD	0.487	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.2% African / African-American · 9,921/74,992 alleles

Filtering AF 13% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.9%

Overall 1.32% 21,248/1,612,818 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.2%	8
Middle Eastern	1.72%	58
Remaining individualsnot grpmax-eligible	1.64%	61
Admixed American	1.41%	71
European (non-Finnish)	0.748%	134
Amishnot grpmax-eligible	0.658%	152
South Asian	0.373%	268
Ashkenazi Jewishnot grpmax-eligible	0.362%	276
Finnishnot grpmax-eligible	0.122%	818

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.Phe1690=
Coding: c.5070C>T
MANE Select: NM_198576
dbSNP: rs17160776
Type: single nucleotide variant
Location: chr1:1050520 (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 1690: the laminin g-like 2 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.Phe1690Leu Uncertain significance ★ 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-phe1690 (accessed [today's date]).

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