Is RELA p.Ser169Ter (c.506C>G) pathogenic?

RELA p.Ser169Ter (c.506C>G) is classified Likely pathogenic in RELA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-25). Absent from gnomAD v4.1; Associated with autoinflammatory disease, familial, Behcet-like-3.

What condition is associated with RELA p.Ser169Ter (c.506C>G)?

RELA p.Ser169Ter (c.506C>G) is associated with autoinflammatory disease, familial, Behcet-like-3 (ClinVar).

How common is RELA p.Ser169Ter (c.506C>G) in the general population?

RELA p.Ser169Ter (c.506C>G) is absent from gnomAD v4.1 (gnomAD).

RELA p.Ser169Ter

Q: How is Combined immunodeficiency due to RELA haploinsufficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.506C>G · VCV4820072

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autoinflammatory disease, familial, Behcet-like-3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 11
REVEL	0.133	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -1.5, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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: RELA
Protein: p.Ser169Ter
Coding: c.506C>G
MANE Select: NM_021975
Type: single nucleotide variant
Location: chr11:65659719 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.52 · 88 PDB
Residue 169: the rhd domain; a β-strand

Full RELA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoinflammatory disease, familial, Behcet-like-3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to RELA haploinsufficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

RELA p.Ser169= Likely benign ★ same residue
RELA p.Arg198Ter Pathogenic/Likely pathogenic ★★ same condition
RELA p.Arg329Ter Pathogenic/Likely pathogenic ★★ same condition
RELA p.Gln372Ter Pathogenic/Likely pathogenic ★★ same condition
RELA p.Arg325Gln Uncertain significance ★★ ⚠ same condition
RELA c.8-10C>T Benign/Likely benign ★★ same condition
RELA p.Asp291Asn Benign/Likely benign ★★ same condition
RELA p.Cys206Ter Likely pathogenic ★ 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/rela-p-ser169ter (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown