Is AMN p.Ser241= (c.723C>T) pathogenic?

AMN p.Ser241= (c.723C>T) is classified Likely benign in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). Very rare (popmax 0.00245%, eas); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.Ser241= (c.723C>T)?

AMN p.Ser241= (c.723C>T) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.Ser241= (c.723C>T) in the general population?

AMN p.Ser241= (c.723C>T) is very rare (popmax 0.00245%, eas) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AMN p.Ser241=

c.723C>T · rs780412383 · VCV2780837

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Conditions

Imerslund-Grasbeck syndrome

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 -0.4	GERP -0.14
Overall
CADD	8.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% East Asian · 1/40,826 alleles

Overall 6.52e-05% 1/1,533,350 alleles · very rare exomes 1/1,381,006 · genomes 0/152,344 · joint denominator

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: AMN
Protein: p.Ser241=
Coding: c.723C>T
MANE Select: NM_030943
dbSNP: rs780412383
Type: single nucleotide variant
Location: chr14:102929499 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.78 · 1 PDB
Residue 241: a β-strand; the vwfc domain

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

Disease context

Imerslund-Grasbeck syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Imerslund-Gräsbeck syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Finland)

Similar variants

AMN c.208-1G>C Pathogenic/Likely pathogenic ★★ same condition
AMN c.296-1G>A Likely pathogenic ★★ same condition
AMN c.44-1G>A Likely pathogenic ★★ same condition
AMN c.760+1G>A Likely pathogenic ★★ same condition
AMN c.844-1G>C Likely pathogenic ★★ same condition
AMN p.Thr41Ile Likely pathogenic ★★ ⚠ same condition
AMN p.Trp391Ter Pathogenic/Likely pathogenic ★★ same condition
AMN c.296-3C>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/amn-p-ser241 (accessed [today's date]).

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