Is RAG1 p.Arg829Ser (c.2487G>T) pathogenic?

RAG1 p.Arg829Ser (c.2487G>T) is classified Uncertain significance in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). AlphaMissense: likely pathogenic (0.889); Ultra-rare (popmax 0.0217%, amr); Associated with Omenn syndrome.

How common is RAG1 p.Arg829Ser (c.2487G>T) in the general population?

RAG1 p.Arg829Ser (c.2487G>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

How is Omenn syndrome inherited?

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

What do computational predictors say about RAG1 p.Arg829Ser (c.2487G>T)?

AlphaMissense predicts likely pathogenic (score 0.889) — an in-silico prediction, not a clinical call.

RAG1 p.Arg829Ser

Q: What condition is associated with RAG1 p.Arg829Ser (c.2487G>T)?

RAG1 p.Arg829Ser (c.2487G>T) is associated with Omenn syndrome, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (ClinVar).

c.2487G>T · rs752304188 · VCV877627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Omenn syndrome

Computational evidence

Protein change
AlphaMissense	0.889	likely pathogenic
REVEL	0.763	pathogenic-leaning
SaProt	LLR -12.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.11, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 2,313 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	22.7	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

Grpmax group 0.0217% Admixed American · 13/60,014 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00124% 20/1,614,110 alleles · ultra-rare exomes 17/1,461,876 · genomes 3/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
European (non-Finnish)	0.000593%	168,579

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: RAG1
Protein: p.Arg829Ser
Coding: c.2487G>T
MANE Select: NM_000448
dbSNP: rs752304188
Type: single nucleotide variant
Location: chr11:36575791 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 829: a UniProt-annotated variant site (in t(-)b(-)nk(+) scid; uncertain significance)

Full RAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Omenn syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive

For Omenn syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

RAG1 p.Arg829_Lys830delinsSerTer Pathogenic ★★★ same residue
RAG1 p.Ala444Val Pathogenic ★★★ same condition
RAG1 p.Arg108Ter Pathogenic ★★★ same condition
RAG1 p.Arg142Ter Pathogenic ★★★ same condition
RAG1 p.Arg394Gln Likely pathogenic ★★★ same condition
RAG1 p.Arg394Trp Pathogenic ★★★ same condition
RAG1 p.Arg396His Pathogenic ★★★ same condition
RAG1 p.Arg404Gln 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/rag1-p-arg829ser (accessed [today's date]).

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