Is AGRN p.Ser215Phe (c.644C>T) pathogenic?

AGRN p.Ser215Phe (c.644C>T) is classified Uncertain significance in AGRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGRN p.Ser215Phe (c.644C>T)?

AGRN p.Ser215Phe (c.644C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AGRN p.Ser215Phe (c.644C>T) in the general population?

AGRN p.Ser215Phe (c.644C>T) is absent from gnomAD v4.1 (gnomAD).

AGRN p.Ser215Phe

c.644C>T · rs1380805752 · VCV3097146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,539,372)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.387	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.94, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,539,372). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGRN
Protein: p.Ser215Phe
Coding: c.644C>T
MANE Select: NM_198576
dbSNP: rs1380805752
Type: single nucleotide variant
Location: chr1:1040797 (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 215: a disulfide bond; the kazal-like 1 domain

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

Similar variants

AGRN p.Ser215Ala Uncertain significance ★★ same residue
AGRN p.Ser215= Likely benign ★ same residue
AGRN p.Ala1012Thr Uncertain significance ★★ same condition
AGRN p.Ala1056Thr Uncertain significance ★★ same condition
AGRN p.Ala1304Thr Uncertain significance ★★ same condition
AGRN p.Ala1325Gly Uncertain significance ★★ same condition
AGRN p.Ala1372Thr Uncertain significance ★★ same condition
AGRN p.Ala1737Val 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-ser215phe (accessed [today's date]).

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