Is AMN c.296-9C>T pathogenic?

AMN c.296-9C>T is classified Benign/Likely benign in AMN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-31). Low-frequency (popmax 1.54%, sas); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN c.296-9C>T?

AMN c.296-9C>T is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN c.296-9C>T in the general population?

AMN c.296-9C>T is low-frequency (popmax 1.54%, sas) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

AMN c.296-9C>T

rs373204347 · VCV463390

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, sas)

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	acceptor -9	acceptor splice region (-9, within the last 20 intronic nt) · inside the BP7-excluded zone
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.028	GERP -1.2
Overall
CADD	4.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.54% South Asian · 1,395/90,652 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.122% 1,951/1,605,570 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.54%	65
Middle Eastern	0.463%	216
Remaining individualsnot grpmax-eligible	0.165%	605
African / African-American	0.131%	765
Admixed American	0.0735%	1,360
East Asian	0.0291%	3,436
European (non-Finnish)	0.0218%	4,587
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,921
Finnishnot grpmax-eligible	0.0121%	8,263

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
Coding: c.296-9C>T
MANE Select: NM_030943
dbSNP: rs373204347
Type: single nucleotide variant
Location: chr14:102928749 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.78 · 1 PDB

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-c-296-minus-9c-t (accessed [today's date]).

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