Is SUN2 p.Asn94Ser (c.281A>G) pathogenic?

SUN2 p.Asn94Ser (c.281A>G) is classified Uncertain significance in SUN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0607); Very rare (popmax 0.00501%, amr).

How common is SUN2 p.Asn94Ser (c.281A>G) in the general population?

SUN2 p.Asn94Ser (c.281A>G) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about SUN2 p.Asn94Ser (c.281A>G)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

SUN2 p.Asn94Ser

c.281A>G · VCV3963996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -3.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 12 kb · p 0.11 · regional, not allelic
Overall
CADD	11.83	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 0.00501% Admixed American · 3/59,926 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,612,292 alleles · very rare exomes 5/1,460,102 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,975
South Asian	0.0022%	45,527
European (non-Finnish)	0.00017%	589,317

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.Asn94Ser
Coding: c.281A>G
MANE Select: NM_015374
Type: single nucleotide variant
Location: chr22:38751215 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 9 PDB
Residue 94: the 'lmna-binding' region

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

Similar variants

SUN2 p.Asn94Lys Uncertain significance ★ ⚠ same residue
SUN2 p.Ala158Thr Uncertain significance ★★ ⚠ same type
SUN2 p.Ala251Val Uncertain significance ★★ ⚠ same type
SUN2 p.Ala508Val Uncertain significance ★★ ⚠ same type
SUN2 p.Ala56Val Uncertain significance ★★ ⚠ same type
SUN2 p.Arg100Gln Uncertain significance ★★ ⚠ same type
SUN2 p.Arg102Gln Uncertain significance ★★ ⚠ same type
SUN2 p.Arg102Trp 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/sun2-p-asn94ser (accessed [today's date]).

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