Is AMER1 p.Ter1136= (c.3408G>A) pathogenic?

AMER1 p.Ter1136= (c.3408G>A) is classified Benign/Likely benign in AMER1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-15). Rare (popmax 0.141%, nfe); Associated with osteopathia striata with cranial sclerosis.

What condition is associated with AMER1 p.Ter1136= (c.3408G>A)?

AMER1 p.Ter1136= (c.3408G>A) is associated with osteopathia striata with cranial sclerosis (ClinVar).

How common is AMER1 p.Ter1136= (c.3408G>A) in the general population?

AMER1 p.Ter1136= (c.3408G>A) is rare (popmax 0.141%, nfe) (gnomAD).

AMER1 p.Ter1136=

c.3408G>A · rs372461050 · VCV720216

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.141%, nfe)

Conditions

osteopathia striata with cranial sclerosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.69, phastCons 1
Overall
CADD	9.352	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

Grpmax group 0.141% European (non-Finnish) · 1,094/774,928 alleles

Filtering AF 0.134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.115% 1,156/1,006,779 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.141%	708
Finnishnot grpmax-eligible	0.0873%	1,145
Remaining individualsnot grpmax-eligible	0.0632%	1,583
African / African-American	0.0221%	4,526
Admixed American	0.00828%	12,072
South Asian	0.0056%	17,853

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.Ter1136=
Coding: c.3408G>A
MANE Select: NM_152424
dbSNP: rs372461050
Type: single nucleotide variant
Location: chrX:64189879 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB

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.Ter1136Gln Uncertain significance ★ same residue
AMER1 p.Arg353Ter Pathogenic ★★ same condition
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.Arg77Trp Uncertain significance ★★ ⚠ same condition
AMER1 p.Gln213Arg 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-ter1136 (accessed [today's date]).

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