Is ASTN2 p.Arg232Ser (c.694C>A) pathogenic?

ASTN2 p.Arg232Ser (c.694C>A) is classified Uncertain significance in ASTN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely pathogenic (0.8679); Very rare (popmax 0.00181%, amr).

How common is ASTN2 p.Arg232Ser (c.694C>A) in the general population?

ASTN2 p.Arg232Ser (c.694C>A) is very rare (popmax 0.00181%, amr) (gnomAD).

What do computational predictors say about ASTN2 p.Arg232Ser (c.694C>A)?

AlphaMissense predicts likely pathogenic (score 0.8679) — an in-silico prediction, not a clinical call.

ASTN2 p.Arg232Ser

c.694C>A · VCV3954816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8679 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00181%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8679	likely pathogenic
REVEL	0.362	indeterminate
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 375 kb · p 0.43 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00181% Admixed American · 1/55,280 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000288% 4/1,389,534 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00181%	55,280
Remaining individualsnot grpmax-eligible	0.00169%	59,322
European (non-Finnish)	0.000176%	568,644

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.Arg232Ser
Coding: c.694C>A
MANE Select: NM_001365068
Type: single nucleotide variant
Location: chr9:117214679 (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

Similar variants

TRIM32 p.Glu232Gln Uncertain significance ★ ⚠ same residue
TRIM32 p.Glu232Gly Uncertain significance ★ same residue
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

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-arg232ser (accessed [today's date]).

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