Is RAG1 p.Ile810Val (c.2428A>G) pathogenic?

RAG1 p.Ile810Val (c.2428A>G) is classified Uncertain significance in RAG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-23). AlphaMissense: likely benign (0.2279); Rare (popmax 0.209%, eas); Associated with Omenn syndrome.

How common is RAG1 p.Ile810Val (c.2428A>G) in the general population?

RAG1 p.Ile810Val (c.2428A>G) is rare (popmax 0.209%, eas) (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.Ile810Val (c.2428A>G)?

AlphaMissense predicts likely benign (score 0.2279) — an in-silico prediction, not a clinical call.

RAG1 p.Ile810Val

Q: What condition is associated with RAG1 p.Ile810Val (c.2428A>G)?

RAG1 p.Ile810Val (c.2428A>G) is associated with Omenn syndrome, combined immunodeficiency with skin granulomas, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (ClinVar).

c.2428A>G · rs61752933 · VCV877626

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2279 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.209%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Omenn syndrome

Computational evidence

Protein change
AlphaMissense	0.2279	likely benign
REVEL	0.622	indeterminate
SaProt	LLR -9.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.51, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 2,313 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.209% East Asian · 94/44,896 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.162%

Overall 0.00595% 96/1,614,102 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.209%	478
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Ile810Val
Coding: c.2428A>G
MANE Select: NM_000448
dbSNP: rs61752933
Type: single nucleotide variant
Location: chr11:36575732 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 810: 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: combined immunodeficiency with skin granulomas 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.Ile810Phe Uncertain significance ★ ⚠ 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-ile810val (accessed [today's date]).

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