Is SUN2 p.Ala289Asp (c.866C>A) pathogenic?

SUN2 p.Ala289Asp (c.866C>A) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.1268); Very rare (popmax 8.47e-05%, nfe).

How common is SUN2 p.Ala289Asp (c.866C>A) in the general population?

SUN2 p.Ala289Asp (c.866C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about SUN2 p.Ala289Asp (c.866C>A)?

AlphaMissense predicts likely benign (score 0.1268) — an in-silico prediction, not a clinical call.

SUN2 p.Ala289Asp

c.866C>A · VCV4177765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1268 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1268	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.8	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 6.2e-05% 1/1,613,438 alleles · very rare exomes 1/1,461,110 · genomes 0/152,328 · joint denominator

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: SUN2
Protein: p.Ala289Asp
Coding: c.866C>A
MANE Select: NM_015374
Type: single nucleotide variant
Location: chr22:38742503 (GRCh38)

Full SUN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/sun2-p-ala289asp (accessed [today's date]).

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