Is ASTN2 p.Ser1052= (c.3156C>T) pathogenic?

ASTN2 p.Ser1052= (c.3156C>T) is classified Benign in ASTN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 1.59%, sas).

How common is ASTN2 p.Ser1052= (c.3156C>T) in the general population?

ASTN2 p.Ser1052= (c.3156C>T) is low-frequency (popmax 1.59%, sas) (gnomAD).

ASTN2 p.Ser1052=

c.3156C>T · rs143407265 · VCV784077

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.59%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.69	GERP -5.6, phastCons 0.99
Overall
CADD	8.553	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.59% South Asian · 1,446/91,082 alleles

Filtering AF 1.52% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.49%

Overall 0.434% 6,998/1,614,126 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.73%	27
South Asiangrpmax	1.59%	63
Middle Eastern	1.53%	65
European (non-Finnish)	0.401%	250
Remaining individualsnot grpmax-eligible	0.389%	257
East Asian	0.345%	290
Admixed American	0.257%	390
Finnishnot grpmax-eligible	0.117%	854
Ashkenazi Jewishnot grpmax-eligible	0.0811%	1,234
African / African-American	0.0613%	1,631

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: ASTN2
Protein: p.Ser1052=
Coding: c.3156C>T
MANE Select: NM_001365068
dbSNP: rs143407265
Type: single nucleotide variant
Location: chr9:116620360 (GRCh38)
Gene constraint: LOEUF 0.473 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 64.93 · 3 PDB
Residue 1052: a disulfide bond

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

Similar variants

TRIM32 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same type
TRIM32 p.Asp487Asn Pathogenic ★★ same type
TRIM32 p.Lys401Ter Pathogenic ★★ same type
TRIM32 p.Tyr226Ter Pathogenic/Likely pathogenic ★★ same type
TRIM32 p.Tyr528Ter Likely pathogenic ★★ same type
ASTN2 p.Val880Gly Uncertain significance ★★ ⚠ same type
TRIM32 c.*152T>G Uncertain significance ★★ same type
TRIM32 p.Ala126Val Uncertain significance ★★ ⚠ same type

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-ser1052 (accessed [today's date]).

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