Is RAG1 p.Arg34Trp (c.100C>T) pathogenic?

RAG1 p.Arg34Trp (c.100C>T) is classified Uncertain significance in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-08). AlphaMissense: likely pathogenic (0.6198); Very rare (popmax 0.00593%, nfe).

How common is RAG1 p.Arg34Trp (c.100C>T) in the general population?

RAG1 p.Arg34Trp (c.100C>T) is very rare (popmax 0.00593%, nfe) (gnomAD).

What do computational predictors say about RAG1 p.Arg34Trp (c.100C>T)?

AlphaMissense predicts likely pathogenic (score 0.6198) — an in-silico prediction, not a clinical call.

RAG1 p.Arg34Trp

c.100C>T · VCV4911245

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6198 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6198	likely pathogenic
REVEL	0.556	indeterminate
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 814 bp · p 0.066 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00593% European (non-Finnish) · 70/1,180,040 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00477% 77/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,858
South Asian	0.00439%	22,769
Admixed American	0.00167%	59,990
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,858

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_000448
Type: single nucleotide variant
Location: chr11:36573404 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 34: the 'interaction with importin alpha-1' region

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

Similar variants

RAG1 p.Arg34Gln Uncertain significance ★★ ⚠ same residue
RAG1 p.Arg34= Likely benign ★ same residue
RAG1 p.Ala444Val Pathogenic ★★★ same type
RAG1 p.Arg108Ter Pathogenic ★★★ same type
RAG1 p.Arg142Ter Pathogenic ★★★ same type
RAG1 p.Arg394Gln Likely pathogenic ★★★ same type
RAG1 p.Arg394Trp Pathogenic ★★★ same type
RAG1 p.Arg396His Pathogenic ★★★ same type

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-arg34trp (accessed [today's date]).

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