Is RELA p.Asp80Val (c.239A>T) pathogenic?

RELA p.Asp80Val (c.239A>T) is classified Uncertain significance in RELA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.8584); Absent from gnomAD v4.1; Associated with autoinflammatory disease, familial, Behcet-like-3.

What condition is associated with RELA p.Asp80Val (c.239A>T)?

RELA p.Asp80Val (c.239A>T) is associated with autoinflammatory disease, familial, Behcet-like-3 (ClinVar).

How common is RELA p.Asp80Val (c.239A>T) in the general population?

RELA p.Asp80Val (c.239A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELA p.Asp80Val (c.239A>T)?

AlphaMissense predicts likely pathogenic (score 0.8584) — an in-silico prediction, not a clinical call.

RELA p.Asp80Val

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.239A>T · VCV4277675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8584 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autoinflammatory disease, familial, Behcet-like-3

Computational evidence

Protein change
AlphaMissense	0.8584	likely pathogenic
REVEL	0.32	indeterminate
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 3,429 bp · p 2.3e-11 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asp80Val
Coding: c.239A>T
MANE Select: NM_021975
Type: single nucleotide variant
Location: chr11:65661783 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.52 · 88 PDB
Residue 80: 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.Asp80Tyr Uncertain significance ★ ⚠ same residue
RELA p.Asp80= 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

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-asp80val (accessed [today's date]).

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