Is RAG1 p.Arg878Ser (c.2634G>C) pathogenic?

RAG1 p.Arg878Ser (c.2634G>C) is classified Uncertain significance in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RAG1 p.Arg878Ser (c.2634G>C)?

RAG1 p.Arg878Ser (c.2634G>C) is associated with Inborn genetic diseases (ClinVar).

How common is RAG1 p.Arg878Ser (c.2634G>C) in the general population?

RAG1 p.Arg878Ser (c.2634G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAG1 p.Arg878Ser (c.2634G>C)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

RAG1 p.Arg878Ser

c.2634G>C · VCV3429956

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic · top 9% in RAG1
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -11.43	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 1.9	GERP -1.9, 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 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: RAG1
Protein: p.Arg878Ser
Coding: c.2634G>C
MANE Select: NM_000448
Type: single nucleotide variant
Location: chr11:36575938 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 878: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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RAG1 p.Gln227Leu Uncertain significance ★★ ⚠ same condition
RAG1 p.Gln911Arg Uncertain significance ★★ ⚠ same condition
RAG1 p.Glu95Lys Uncertain significance ★★ ⚠ same condition
RAG1 p.His636Arg Uncertain significance ★★ ⚠ same condition
RAG1 p.His769Arg Uncertain significance ★★ ⚠ same condition
RAG1 p.Ile815Met Uncertain significance ★★ ⚠ 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-arg878ser (accessed [today's date]).

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