Is RALGAPB p.Glu428= (c.1284A>G) pathogenic?

RALGAPB p.Glu428= (c.1284A>G) is classified Benign in RALGAPB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Low-frequency (popmax 1.52%, afr); Associated with RALGAPB-related disorder.

What condition is associated with RALGAPB p.Glu428= (c.1284A>G)?

RALGAPB p.Glu428= (c.1284A>G) is associated with RALGAPB-related disorder (ClinVar).

How common is RALGAPB p.Glu428= (c.1284A>G) in the general population?

RALGAPB p.Glu428= (c.1284A>G) is low-frequency (popmax 1.52%, afr) (gnomAD).

RALGAPB p.Glu428=

c.1284A>G · rs41276946 · VCV3033905

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.52%, afr)

Conditions

RALGAPB-related disorder

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 1.9	GERP 2.7, phastCons 1
Overall
CADD	6.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.52% African / African-American · 1,138/74,996 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 0.0812% 1,311/1,613,914 alleles · low-frequency exomes 676/1,461,660 · genomes 635/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.52%	66
Remaining individualsnot grpmax-eligible	0.0896%	1,116
Admixed American	0.0733%	1,364
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.00551%	18,151
South Asian	0.00549%	18,216

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: RALGAPB
Protein: p.Glu428=
Coding: c.1284A>G
MANE Select: NM_020336
dbSNP: rs41276946
Type: single nucleotide variant
Location: chr20:38517867 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.28 · 1 PDB
Residue 428: the 'disordered' region

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

Disease context

RALGAPB-related disorder

Similar variants

RALGAPB p.Pro271Ala Uncertain significance ★ ⚠ same condition
RALGAPB p.Val234= Uncertain significance ★ same condition
RALGAPB p.Lys84Arg Uncertain significance ⚠ same condition
RALGAPB c.554-10T>C Benign same condition
RALGAPB p.Ala998= Benign same condition
RALGAPB p.Asn276His Benign same condition
RALGAPB p.Asp1284= Benign same condition
RALGAPB p.His1191Tyr Benign 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/ralgapb-p-glu428 (accessed [today's date]).

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