SUN1 p.Cys376=
c.1128C>T · rs1294019181 · VCV779494
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.057 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.64 | GERP 0.87, phastCons 0.007 |
| Overall | ||
| CADD | 3.025 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000744%
12/1,613,946 alleles · ultra-rare
exomes 12/1,461,616 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| East Asian | 0.00223% | 44,882 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| European (non-Finnish) | 0.000678% | 147,506 |
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
- SUN1
- Protein
- p.Cys376=
- Coding
- c.1128C>T
- MANE Select
- NM_001130965
- dbSNP
- rs1294019181
- Type
- single nucleotide variant
- Location
- chr7:853483 (GRCh38)
- Gene constraint
- LOEUF 0.712 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99 · 8 PDB
- Residue 376
- an α-helix
Similar variants
- SUN1 p.Cys376Ser Uncertain significance ★ same residue
- SUN1 p.Cys376Tyr Uncertain significance ★ same residue
- SUN1 p.Ala179Thr Uncertain significance ★★ same type
- SUN1 p.Ala203Thr Uncertain significance ★★ same type
- SUN1 p.Ala232Val Uncertain significance ★★ same type
- SUN1 p.Ala236Thr Uncertain significance ★★ same type
- SUN1 p.Ala255Thr Uncertain significance ★★ same type
- SUN1 p.Ala256Val 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/sun1-p-cys376 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown