Is RAG1 p.Pro1028= (c.3084A>G) pathogenic?

RAG1 p.Pro1028= (c.3084A>G) is classified Likely benign in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-20). Very rare (popmax 0.00223%, eas); Associated with combined immunodeficiency with skin granulomas.

What condition is associated with RAG1 p.Pro1028= (c.3084A>G)?

RAG1 p.Pro1028= (c.3084A>G) 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.Pro1028= (c.3084A>G) in the general population?

RAG1 p.Pro1028= (c.3084A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Combined immunodeficiency with granulomatosis inherited?

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

RAG1 p.Pro1028=

c.3084A>G · rs1238573903 · VCV1158325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.5	GERP -5.6
Overall
CADD	0.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,894 alleles

Overall 0.000186% 3/1,614,072 alleles · very rare exomes 2/1,461,834 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,096

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.Pro1028=
Coding: c.3084A>G
MANE Select: NM_000448
dbSNP: rs1238573903
Type: single nucleotide variant
Location: chr11:36576388 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 1028: 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.Pro1028Gln Uncertain significance ★★ ⚠ same residue
RAG1 p.Pro1028Leu 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

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-pro1028 (accessed [today's date]).

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