SPEG p.Arg600=
c.1800G>C · rs60593157 · VCV287262
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 17.4%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 0.23, phastCons 1 |
| Overall | ||
| CADD | 8.532 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.4%
African / African-American · 11,989/68,776 alleles
Filtering AF
17.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.1%
Overall
4.43%
66,962/1,511,136 alleles · common
exomes 55,715/1,359,034 · genomes 11,247/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 17.4% | 6 |
| Middle Eastern | 5.52% | 18 |
| Remaining individualsnot grpmax-eligible | 4.9% | 20 |
| South Asian | 4.49% | 22 |
| European (non-Finnish) | 3.96% | 25 |
| Admixed American | 3.66% | 27 |
| Ashkenazi Jewishnot grpmax-eligible | 3.33% | 30 |
| Amishnot grpmax-eligible | 2.19% | 46 |
| Finnishnot grpmax-eligible | 1.34% | 74 |
| East Asian | 0.011% | 9,094 |
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
- SPEG
- Protein
- p.Arg600=
- Coding
- c.1800G>C
- MANE Select
- NM_005876
- dbSNP
- rs60593157
- Type
- single nucleotide variant
- Location
- chr2:219448958 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 600
- the 'disordered' region
Similar variants
- SPEG p.Arg1467Ter Likely pathogenic ★★ same type
- SPEG p.Ser131Ter Pathogenic/Likely pathogenic ★★ same type
- SPEG c.3301+5G>A Uncertain significance ★★ same type
- SPEG c.478+5G>A Uncertain significance ★★ same type
- SPEG p.Ala121Thr Uncertain significance ★★ same type
- SPEG p.Ala1249Thr Uncertain significance ★★ ⚠ same type
- SPEG p.Ala1334Val Uncertain significance ★★ ⚠ same type
- SPEG p.Ala154Asp 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/speg-p-arg600 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown