Is RALGAPB p.Pro1027Ala (c.3079C>G) pathogenic?

RALGAPB p.Pro1027Ala (c.3079C>G) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1741); Ultra-rare (popmax 0.0217%, amr).

How common is RALGAPB p.Pro1027Ala (c.3079C>G) in the general population?

RALGAPB p.Pro1027Ala (c.3079C>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about RALGAPB p.Pro1027Ala (c.3079C>G)?

AlphaMissense predicts likely benign (score 0.1741) — an in-silico prediction, not a clinical call.

RALGAPB p.Pro1027Ala

c.3079C>G · rs141179561 · VCV2344025

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1741 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1741	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 63 kb · p 1.7e-18 · regional, not allelic
Overall
CADD	23.5	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 0.0217% Admixed American · 13/59,992 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.0236% 381/1,613,722 alleles · ultra-rare exomes 344/1,461,532 · genomes 37/152,190 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.939%	106
Remaining individualsnot grpmax-eligible	0.0768%	1,301
Admixed Americangrpmax	0.0217%	4,615
Middle Eastern	0.0164%	6,084
European (non-Finnish)	0.00331%	30,250
African / African-American	0.00267%	37,458

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1027Ala
Coding: c.3079C>G
MANE Select: NM_020336
dbSNP: rs141179561
Type: single nucleotide variant
Location: chr20:38551140 (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-pro1027ala (accessed [today's date]).

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