Is RAG1 p.Val990= (c.2970C>A) pathogenic?

RAG1 p.Val990= (c.2970C>A) is classified Likely benign in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). Absent from gnomAD v4.1; Associated with combined immunodeficiency with skin granulomas.

What condition is associated with RAG1 p.Val990= (c.2970C>A)?

RAG1 p.Val990= (c.2970C>A) is associated with combined immunodeficiency with skin granulomas, severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive (ClinVar).

How common is RAG1 p.Val990= (c.2970C>A) in the general population?

RAG1 p.Val990= (c.2970C>A) is absent from gnomAD v4.1 (gnomAD).

How is Combined immunodeficiency with granulomatosis inherited?

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

RAG1 p.Val990=

c.2970C>A · rs2133298485 · VCV1577063

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,036)

Conditions

combined immunodeficiency with skin granulomas

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.003	GERP -3, phastCons 0.001
Overall
CADD	1.389	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,036). 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: RAG1
Protein: p.Val990=
Coding: c.2970C>A
MANE Select: NM_000448
dbSNP: rs2133298485
Type: single nucleotide variant
Location: chr11:36576274 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 990: a UniProt-annotated variant site (in t(-)b(-)nk(+) scid; uncertain significance); a UniProt-annotated variant site (in t(-)b(-)nk(+) scid; uncertain significance; also found in patients with an atypical form of severe combined immunodeficiency/omenn syndrome; uncertain significance; loss of recombination activity); a UniProt-annotated variant site (in t(-)b(-)nk(+) scid; decreased recombination activity)

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

Disease context

combined immunodeficiency with skin granulomas — 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 Combined immunodeficiency with granulomatosis (Orphanet):

Inheritance: Autosomal recessive

Similar variants

RAG1 p.Val990Ile 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-val990 (accessed [today's date]).

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