Is ASTN2 p.Ser180= (c.540C>T) pathogenic?

ASTN2 p.Ser180= (c.540C>T) is classified Benign in ASTN2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Common (popmax 18.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ASTN2-related disorder.

What condition is associated with ASTN2 p.Ser180= (c.540C>T)?

ASTN2 p.Ser180= (c.540C>T) is associated with ASTN2-related disorder (ClinVar).

ASTN2 p.Ser180=

Q: How common is ASTN2 p.Ser180= (c.540C>T) in the general population?

ASTN2 p.Ser180= (c.540C>T) is common (popmax 18.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.540C>T · rs2297697 · VCV3042320

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 18.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ASTN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.6	GERP -3.8
Overall
CADD	0.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.7% East Asian · 8,372/44,872 alleles

Filtering AF 18.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.2%

Overall 1.29% 20,872/1,614,170 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	18.7%	5
Admixed American	7.19%	14
South Asian	4.87%	21
Remaining individualsnot grpmax-eligible	1.8%	55
Ashkenazi Jewishnot grpmax-eligible	1.4%	71
African / African-American	0.36%	278
Middle Eastern	0.33%	303
European (non-Finnish)	0.16%	626
Finnishnot grpmax-eligible	0.0515%	1,941

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: ASTN2
Protein: p.Ser180=
Coding: c.540C>T
MANE Select: NM_001365068
dbSNP: rs2297697
Type: single nucleotide variant
Location: chr9:117291416 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 64.93 · 3 PDB

Full ASTN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ASTN2-related disorder

Similar variants

TRIM32 p.Arg180Thr Uncertain significance ★ same residue
TRIM32 p.Arg180= Likely benign ★ same residue
TRIM32 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same condition
TRIM32 p.Asp487Asn Pathogenic ★★ same condition
TRIM32 p.Tyr226Ter Pathogenic/Likely pathogenic ★★ same condition
ASTN2 p.Val880Gly Uncertain significance ★★ ⚠ same condition
TRIM32 p.Arg147Gln Uncertain significance ★★ ⚠ same condition
TRIM32 p.Arg238Leu 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/astn2-p-ser180 (accessed [today's date]).

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