Is AMER1 p.Arg353Ter (c.1057C>T) pathogenic?

AMER1 p.Arg353Ter (c.1057C>T) is classified Pathogenic in AMER1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-01-13). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AMER1 p.Arg353Ter (c.1057C>T)?

AMER1 p.Arg353Ter (c.1057C>T) is associated with Inborn genetic diseases, osteopathia striata with cranial sclerosis (ClinVar).

How common is AMER1 p.Arg353Ter (c.1057C>T) in the general population?

AMER1 p.Arg353Ter (c.1057C>T) is absent from gnomAD v4.1 (gnomAD).

AMER1 p.Arg353Ter

c.1057C>T · rs137852216 · VCV10707

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,211,848)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.13, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,211,848). 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.Arg353Ter
Coding: c.1057C>T
MANE Select: NM_152424
dbSNP: rs137852216
Type: single nucleotide variant
Location: chrX:64192230 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 353: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: osteopathia striata with cranial sclerosis

Similar variants

AMER1 p.Arg353Gln Uncertain significance ★ ⚠ same residue
AMER1 p.Arg358Ter Pathogenic ★★ same condition
AMER1 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same condition
AMER1 p.Gln189Ter Pathogenic ★★ same condition
AMER1 p.Gln335Ter Pathogenic ★★ same condition
AMER1 p.Ala202Gly Uncertain significance ★★ ⚠ same condition
AMER1 p.Arg1113Met Uncertain significance ★★ ⚠ same condition
AMER1 p.Arg586Gln 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-arg353ter (accessed [today's date]).

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