SIM1 p.Asp202Glu
c.606C>A · VCV3318541
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
AlphaMissense
ambiguous
0.4659 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4659 | ambiguous |
|---|---|---|
| REVEL | 0.18 | moderately benign-leaning |
| SaProt | LLR -8.12 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.98 | GERP -4.9 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 1,473 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 3.122 | 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
- SIM1
- Protein
- p.Asp202Glu
- Coding
- c.606C>A
- MANE Select
- NM_005068
- Type
- single nucleotide variant
- Location
- chr6:100448616 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70
Similar variants
- SIM1 p.Cys434Ter Pathogenic ★★ same condition
- SIM1 p.Ala495Gly Uncertain significance ★★ ⚠ same condition
- SIM1 p.Arg548Gln Uncertain significance ★★ ⚠ same condition
- SIM1 p.Cys605Tyr Uncertain significance ★★ ⚠ same condition
- SIM1 p.Glu552Lys Uncertain significance ★★ ⚠ same condition
- SIM1 p.Glu617Lys Uncertain significance ★★ ⚠ same condition
- SIM1 p.Glu725Lys Uncertain significance ★★ same condition
- SIM1 p.Gly203Cys Uncertain significance ★★ ⚠ same condition
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/sim1-p-asp202glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown