Is AMER1 p.Pro224fs (c.671del) pathogenic?

AMER1 p.Pro224fs (c.671del) is classified Pathogenic in AMER1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2009-01-01). Absent from gnomAD; Associated with osteopathia striata with cranial sclerosis.

What condition is associated with AMER1 p.Pro224fs (c.671del)?

AMER1 p.Pro224fs (c.671del) is associated with osteopathia striata with cranial sclerosis (ClinVar).

How common is AMER1 p.Pro224fs (c.671del) in the general population?

AMER1 p.Pro224fs (c.671del) is absent from gnomAD (gnomAD).

AMER1 p.Pro224fs

c.671del · rs1569192315 · VCV10704

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

osteopathia striata with cranial sclerosis

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 0.12	GERP -3.4

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMER1
Protein: p.Pro224fs
Coding: c.671del
MANE Select: NM_152424
dbSNP: rs1569192315
Type: Deletion
Location: chrX:64192616 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 224: the 'disordered' region

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

Disease context

osteopathia striata with cranial sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMER1 p.Gln232fs Pathogenic ★★ same condition
AMER1 p.Glu462fs Likely pathogenic ★ same condition
AMER1 p.Gly186_Ala187insTer Pathogenic ★ same condition
AMER1 p.His104fs Pathogenic ★ same condition
AMER1 p.Lys292_Val293insTer Pathogenic ★ same condition
AMER1 p.Phe60fs Pathogenic ★ same condition
AMER1 p.Tyr526fs Likely pathogenic ★ same condition
AMER1 p.Glu219fs Likely pathogenic 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-pro224fs (accessed [today's date]).

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