Is ATE1 p.Ser412= (c.1236A>G) pathogenic?

ATE1 p.Ser412= (c.1236A>G) is classified Benign in ATE1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 94.1%, mid) — too common for a highly-penetrant pathogenic allele; Associated with ATE1-related disorder.

What condition is associated with ATE1 p.Ser412= (c.1236A>G)?

ATE1 p.Ser412= (c.1236A>G) is associated with ATE1-related disorder (ClinVar).

ATE1 p.Ser412=

Q: How common is ATE1 p.Ser412= (c.1236A>G) in the general population?

ATE1 p.Ser412= (c.1236A>G) is common (popmax 94.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1236A>G · rs4237536 · VCV3060294

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 94.1%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

ATE1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.043	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4.9
Overall
CADD	2.222	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 94.1% Middle Eastern · 5,342/5,676 alleles

Filtering AF 92% ClinGen BA1/BS1 input FAF95, joint · FAF99 91.9%

Overall 91.3% 1,438,026/1,575,284 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	95.4%	1
Ashkenazi Jewishnot grpmax-eligible	95.2%	1
Middle Easterngrpmax	94.1%	1
Finnishnot grpmax-eligible	93.1%	1
East Asian	92.4%	1
European (non-Finnish)	92.1%	1
Remaining individualsnot grpmax-eligible	91.4%	1
South Asian	89%	1
African / African-American	87.1%	1
Admixed American	78.2%	1

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ATE1
Protein: p.Ser412=
Coding: c.1236A>G
MANE Select: NM_001001976
dbSNP: rs4237536
Type: single nucleotide variant
Location: chr10:121836739 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.56 · 2 PDB

Full ATE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ATE1-related disorder

Similar variants

ATE1 c.1157+7T>C Benign same condition
ATE1 c.942+1004C>T Likely benign same condition
ATE1 c.*8A>G Benign same condition
ATE1 p.Ala123= Likely benign same condition
ATE1 p.Asp357= Likely benign same condition
ATE1 p.Leu101= Benign same condition
ATE1 p.Phe3= Benign same condition
ATE1 p.Pro457= Benign 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/ate1-p-ser412 (accessed [today's date]).

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