SPEG p.Pro1174=
c.3522C>T · rs376913006 · VCV1610170
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -3 |
| Overall | ||
| CADD | 0.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
Admixed American · 27/60,000 alleles
Filtering AF
0.0317%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0273%
Overall
0.00508%
82/1,613,836 alleles · ultra-rare
exomes 74/1,461,642 · genomes 8/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.045% | 2,222 |
| African / African-American | 0.00534% | 18,732 |
| European (non-Finnish) | 0.00415% | 24,082 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| South Asian | 0.0011% | 91,082 |
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.Pro1174=
- Coding
- c.3522C>T
- MANE Select
- NM_005876
- dbSNP
- rs376913006
- Type
- single nucleotide variant
- Location
- chr2:219469186 (GRCh38)
- Gene constraint
- LOEUF 0.514 · pLI <0.01 (gnomAD)
- Residue 1174
- 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-pro1174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown