Is AMN p.Met55Ile (c.165G>A) pathogenic?

AMN p.Met55Ile (c.165G>A) is classified Benign/Likely benign in AMN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: ambiguous (0.403); Low-frequency (popmax 1.62%, afr); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with AMN p.Met55Ile (c.165G>A)?

AMN p.Met55Ile (c.165G>A) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is AMN p.Met55Ile (c.165G>A) in the general population?

AMN p.Met55Ile (c.165G>A) is low-frequency (popmax 1.62%, afr) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

What do computational predictors say about AMN p.Met55Ile (c.165G>A)?

AlphaMissense predicts ambiguous (score 0.403) — an in-silico prediction, not a clinical call.

AMN p.Met55Ile

c.165G>A · rs61731158 · VCV618526

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.403 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.62%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
AlphaMissense	0.403	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR 0.28	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -0.026, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 7,988 bp · p 0.14 · regional, not allelic
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.62% African / African-American · 1,216/75,058 alleles

Filtering AF 1.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.51%

Overall 0.0867% 1,398/1,613,200 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.62%	62
Admixed American	0.117%	858
Remaining individualsnot grpmax-eligible	0.114%	880
Middle Eastern	0.066%	1,516
South Asian	0.00549%	18,217
European (non-Finnish)	0.00263%	38,065
Finnishnot grpmax-eligible	0.00159%	63,052

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.Met55Ile
Coding: c.165G>A
MANE Select: NM_030943
dbSNP: rs61731158
Type: single nucleotide variant
Location: chr14:102923937 (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 55: a disulfide bond

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-met55ile (accessed [today's date]).

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