Is RALGAPB p.Asp1095Val (c.3284A>T) pathogenic?

RALGAPB p.Asp1095Val (c.3284A>T) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.1573); Ultra-rare (popmax 0.0329%, mid).

How common is RALGAPB p.Asp1095Val (c.3284A>T) in the general population?

RALGAPB p.Asp1095Val (c.3284A>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about RALGAPB p.Asp1095Val (c.3284A>T)?

AlphaMissense predicts likely benign (score 0.1573) — an in-silico prediction, not a clinical call.

RALGAPB p.Asp1095Val

c.3284A>T · VCV4150224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1573 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1573	likely benign
REVEL	0.478	indeterminate
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 24 kb · p 7.4e-05 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00254% 41/1,613,700 alleles · ultra-rare exomes 39/1,461,686 · genomes 2/152,014 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.00195%	51,297

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.Asp1095Val
Coding: c.3284A>T
MANE Select: NM_020336
Type: single nucleotide variant
Location: chr20:38553988 (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-asp1095val (accessed [today's date]).

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