Is AMER1 p.Pro237fs (c.705del) pathogenic?

AMER1 p.Pro237fs (c.705del) is classified Pathogenic in AMER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-10-27). Very rare (popmax 9.26e-05%).

How common is AMER1 p.Pro237fs (c.705del) in the general population?

AMER1 p.Pro237fs (c.705del) is very rare (popmax 9.26e-05%) (gnomAD).

AMER1 p.Pro237fs

c.705del · rs1131691649 · VCV429881

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.26e-05%)

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 0.82	GERP -0.23

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.26e-05%

Overall 9.26e-05% 1/1,080,104 alleles · very rare

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: AMER1
Protein: p.Pro237fs
Coding: c.705del
MANE Select: NM_152424
dbSNP: rs1131691649
Type: Deletion
Location: chrX:64192582 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 237: the 'disordered' region

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

Similar variants

AMER1 p.Arg497fs Pathogenic/Likely pathogenic ★★ same type
AMER1 p.Gln232fs Pathogenic ★★ same type
AMER1 p.Leu406fs Pathogenic ★★ same type
AMER1 p.Lys292fs Pathogenic ★★ same type
AMER1 p.Asp315fs Pathogenic ★ same type
AMER1 p.Asp481fs Pathogenic ★ same type
AMER1 p.Cys125fs Pathogenic ★ same type
AMER1 p.Cys216fs Pathogenic ★ same type

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-pro237fs (accessed [today's date]).

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