Is RELA p.Ser437Ter (c.1310C>G) pathogenic?

RELA p.Ser437Ter (c.1310C>G) is classified Likely pathogenic in RELA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). No allele count reported in gnomAD v4.1 (AN 1,530,630); Associated with autoinflammatory disease, familial, Behcet-like-3.

What condition is associated with RELA p.Ser437Ter (c.1310C>G)?

RELA p.Ser437Ter (c.1310C>G) is associated with autoinflammatory disease, familial, Behcet-like-3 (ClinVar).

How common is RELA p.Ser437Ter (c.1310C>G) in the general population?

RELA p.Ser437Ter (c.1310C>G) is no allele count reported in gnomAD v4.1 (AN 1,530,630) (gnomAD).

RELA p.Ser437Ter

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.1310C>G · rs749716796 · VCV3068723

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,530,630)

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	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Overall
CADD	36.0	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

No allele count reported in gnomAD v4.1 (AN 1,530,630). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RELA
Protein: p.Ser437Ter
Coding: c.1310C>G
MANE Select: NM_021975
dbSNP: rs749716796
Type: single nucleotide variant
Location: chr11:65654724 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.52 · 88 PDB
Residue 437: a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance); the 'transcriptional activation domain 1' region

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.Ser437Leu Uncertain significance ★ ⚠ 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-ser437ter (accessed [today's date]).

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