Is RALGAPB p.Ala998= (c.2994A>G) pathogenic?

RALGAPB p.Ala998= (c.2994A>G) is classified Benign in RALGAPB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-26). Common (popmax 17.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with RALGAPB-related disorder.

What condition is associated with RALGAPB p.Ala998= (c.2994A>G)?

RALGAPB p.Ala998= (c.2994A>G) is associated with RALGAPB-related disorder (ClinVar).

RALGAPB p.Ala998=

Q: How common is RALGAPB p.Ala998= (c.2994A>G) in the general population?

RALGAPB p.Ala998= (c.2994A>G) is common (popmax 17.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2994A>G · rs805548 · VCV3037681

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 17.9%, afr) — too common for a highly-penetrant pathogenic allele

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 5.4	GERP 1.9, phastCons 1
Overall
CADD	12.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.9% African / African-American · 13,372/74,912 alleles

Filtering AF 17.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.5%

Overall 3.61% 58,259/1,611,756 alleles · common exomes 47,488/1,459,462 · genomes 10,771/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	17.9%	6
Ashkenazi Jewishnot grpmax-eligible	4.04%	25
Remaining individualsnot grpmax-eligible	3.79%	26
European (non-Finnish)	3.18%	31
Admixed American	3.13%	32
Middle Eastern	3.02%	33
Finnishnot grpmax-eligible	2.05%	49
Amishnot grpmax-eligible	0.658%	152
South Asian	0.476%	210
East Asian	0.00446%	22,440

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.Ala998=
Coding: c.2994A>G
MANE Select: NM_020336
dbSNP: rs805548
Type: single nucleotide variant
Location: chr20:38548780 (GRCh38)
Gene constraint: LOEUF 0.202 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 75.28 · 1 PDB

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.Asn276His Benign same condition
RALGAPB p.Asp1284= Benign same condition
RALGAPB p.Glu428= 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-ala998 (accessed [today's date]).

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