SPEG p.Pro328=
c.984C>T · rs187565836 · VCV287261
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.97%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.052 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.58 | GERP -1.1, phastCons 0.12 |
| Overall | ||
| CADD | 7.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.97%
African / African-American · 2,223/74,882 alleles
Filtering AF
2.87%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.82%
Overall
0.154%
2,470/1,607,544 alleles · low-frequency
exomes 1,166/1,455,232 · genomes 1,304/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.97% | 34 |
| Admixed American | 0.171% | 584 |
| Remaining individualsnot grpmax-eligible | 0.161% | 621 |
| Middle Eastern | 0.0663% | 1,509 |
| South Asian | 0.0221% | 4,533 |
| European (non-Finnish) | 0.00178% | 56,055 |
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.Pro328=
- Coding
- c.984C>T
- MANE Select
- NM_005876
- dbSNP
- rs187565836
- Type
- single nucleotide variant
- Location
- chr2:219448142 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 328
- 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-pro328 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown