Is AMER1 p.Pro197fs (c.588del) pathogenic?

AMER1 p.Pro197fs (c.588del) is classified Likely pathogenic in AMER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-12-05). Associated with AMER1-related disorder.

What condition is associated with AMER1 p.Pro197fs (c.588del)?

AMER1 p.Pro197fs (c.588del) is associated with AMER1-related disorder (ClinVar).

AMER1 p.Pro197fs

c.588del · VCV4951128

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

AMER1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.57	GERP -3.2, phastCons 0.11

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AMER1
Protein: p.Pro197fs
Coding: c.588del
MANE Select: NM_152424
Type: Deletion
Location: chrX:64192699 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 197: the 'disordered' region

Full AMER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AMER1-related disorder

Similar variants

AMER1 p.Ser129fs Likely pathogenic ★ same condition
AMER1 p.Pro197Thr Uncertain significance ★ ⚠ same residue
AMER1 p.Glu191Ter Pathogenic/Likely pathogenic ★★ same condition
AMER1 p.Cys125Ter Likely pathogenic ★ same condition
AMER1 p.Glu557fs Likely pathogenic ★ same condition
AMER1 p.Glu7Ter Likely pathogenic ★ same condition
AMER1 p.Ala610Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
AMER1 p.Cys964Ser 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/amer1-p-pro197fs (accessed [today's date]).

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