Is RAG1 p.Asp429Val (c.1286A>T) pathogenic?

RAG1 p.Asp429Val (c.1286A>T) is classified Uncertain significance in RAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). AlphaMissense: likely pathogenic (0.8863); Very rare (popmax 8.47e-05%, nfe).

How common is RAG1 p.Asp429Val (c.1286A>T) in the general population?

RAG1 p.Asp429Val (c.1286A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about RAG1 p.Asp429Val (c.1286A>T)?

AlphaMissense predicts likely pathogenic (score 0.8863) — an in-silico prediction, not a clinical call.

RAG1 p.Asp429Val

c.1286A>T · rs104894292 · VCV3233811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8863 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8863	likely pathogenic
REVEL	0.942	strongly pathogenic-leaning
SaProt	LLR -15.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 2,313 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	27.2	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,050 alleles

Overall 6.19e-05% 1/1,614,208 alleles · very rare exomes 1/1,461,876 · genomes 0/152,332 · joint denominator

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.Asp429Val
Coding: c.1286A>T
MANE Select: NM_000448
dbSNP: rs104894292
Type: single nucleotide variant
Location: chr11:36574590 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.68
Residue 429: a DNA-binding region; a UniProt-annotated variant site (in os)

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

Similar variants

RAG1 p.Asp429Gly Pathogenic 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
RAG1 p.Arg404Gln 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-asp429val (accessed [today's date]).

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