ARCN1 p.Asp321Glu
c.963T>A · VCV4534274
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4989 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4989 | ambiguous |
|---|---|---|
| REVEL | 0.158 | moderately benign-leaning |
| SaProt | LLR -4.52 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -1.6, phastCons 1 |
| Regional constraint | o/e 0.82 | unconstrained · MANE · 17 kb · p 0.00011 · regional, not allelic |
| Overall | ||
| CADD | 17.6 | 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
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ARCN1
- Protein
- p.Asp321Glu
- Coding
- c.963T>A
- MANE Select
- NM_001655
- Type
- single nucleotide variant
- Location
- chr11:118590485 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 84.25
- Residue 321
- the mhd domain
Similar variants
- ARCN1 p.Asp321Gly Uncertain significance ★ same residue
- ARCN1 c.654-15A>G Pathogenic/Likely pathogenic ★★ same type
- ARCN1 p.Arg170Ter Pathogenic ★★ same type
- ARCN1 p.Arg312Ter Pathogenic ★★ same type
- ARCN1 p.Arg435Ter Pathogenic/Likely pathogenic ★★ same type
- ARCN1 p.Ala169Val Uncertain significance ★★ ⚠ same type
- ARCN1 p.Arg160His Uncertain significance ★★ ⚠ same type
- ARCN1 p.Arg161His 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/arcn1-p-asp321glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown