RELA p.Ser377=
c.1131G>A · rs7116571 · VCV1170130
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 9.75%, 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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3 |
| Overall | ||
| CADD | 3.837 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.75%
African / African-American · 7,293/74,826 alleles
Filtering AF
9.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.48%
Overall
0.576%
9,162/1,591,820 alleles · common
exomes 4,895/1,439,604 · genomes 4,267/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.75% | 10 |
| Admixed American | 0.89% | 112 |
| Remaining individualsnot grpmax-eligible | 0.877% | 114 |
| Middle Eastern | 0.729% | 137 |
| Amishnot grpmax-eligible | 0.658% | 152 |
| European (non-Finnish) | 0.0641% | 1,559 |
| South Asian | 0.0341% | 2,928 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00344% | 29,062 |
| Finnishnot grpmax-eligible | 0.00161% | 62,012 |
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
- RELA
- Protein
- p.Ser377=
- Coding
- c.1131G>A
- MANE Select
- NM_021975
- dbSNP
- rs7116571
- Type
- single nucleotide variant
- Location
- chr11:65654903 (GRCh38)
- Gene constraint
- LOEUF 0.4 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.52 · 88 PDB
- Residue 377
- the 'transcriptional activation domain 3' region; a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance)
Similar variants
- RELA p.Ser377Leu Uncertain significance ★★ ⚠ same residue
- RELA p.Arg198Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Arg236Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Arg329Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Gln372Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Ala264Val Uncertain significance ★★ ⚠ same type
- RELA p.Ala404Pro Uncertain significance ★★ ⚠ same type
- RELA p.Ala404Thr 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/rela-p-ser377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown