Is RALGAPB p.Glu481Val (c.1442A>T) pathogenic?

RALGAPB p.Glu481Val (c.1442A>T) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.3877); Ultra-rare (popmax 0.01%, amr).

How common is RALGAPB p.Glu481Val (c.1442A>T) in the general population?

RALGAPB p.Glu481Val (c.1442A>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about RALGAPB p.Glu481Val (c.1442A>T)?

AlphaMissense predicts ambiguous (score 0.3877) — an in-silico prediction, not a clinical call.

RALGAPB p.Glu481Val

c.1442A>T · VCV4575518

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3877 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3877	ambiguous
REVEL	0.245	benign-leaning
SaProt	LLR -6.61	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 5.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 63 kb · p 1.7e-18 · regional, not allelic
Overall
CADD	24.7	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 0.01% Admixed American · 6/59,998 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00062% 10/1,613,958 alleles · ultra-rare exomes 8/1,461,824 · genomes 2/152,134 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,000
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000254%	393,331

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.Glu481Val
Coding: c.1442A>T
MANE Select: NM_020336
Type: single nucleotide variant
Location: chr20:38521521 (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

Similar variants

RALGAPB p.Asp736Asn Uncertain significance ★★ ⚠ same type
RALGAPB p.Glu1365= Benign ★★ same type
RALGAPB c.4142+1G>A Pathogenic ★ same type
RALGAPB p.Arg775Leu Likely pathogenic ★ ⚠ same type
RALGAPB p.Ala1067Thr Uncertain significance ★ ⚠ same type
RALGAPB p.Ala1257Asp Uncertain significance ★ ⚠ same type
RALGAPB p.Ala1429Val Uncertain significance ★ same type
RALGAPB p.Ala243Gly Uncertain significance ★ ⚠ 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/ralgapb-p-glu481val (accessed [today's date]).

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