Is RALGAPB p.Pro271Ala (c.811C>G) pathogenic?

RALGAPB p.Pro271Ala (c.811C>G) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-26). AlphaMissense: likely benign (0.2547); Very rare (popmax 0.000594%, nfe); Associated with RALGAPB-related disorder.

What condition is associated with RALGAPB p.Pro271Ala (c.811C>G)?

RALGAPB p.Pro271Ala (c.811C>G) is associated with RALGAPB-related disorder (ClinVar).

How common is RALGAPB p.Pro271Ala (c.811C>G) in the general population?

RALGAPB p.Pro271Ala (c.811C>G) is very rare (popmax 0.000594%, nfe) (gnomAD).

What do computational predictors say about RALGAPB p.Pro271Ala (c.811C>G)?

AlphaMissense predicts likely benign (score 0.2547) — an in-silico prediction, not a clinical call.

RALGAPB p.Pro271Ala

c.811C>G · rs2085858141 · VCV2631650

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RALGAPB-related disorder

Computational evidence

Protein change
AlphaMissense	0.2547	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 5.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 63 kb · p 1.7e-18 · regional, not allelic
Overall
CADD	26.8	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 0.000594% European (non-Finnish) · 7/1,179,360 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,438 alleles · very rare exomes 7/1,461,136 · genomes 0/152,302 · joint denominator

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.Pro271Ala
Coding: c.811C>G
MANE Select: NM_020336
dbSNP: rs2085858141
Type: single nucleotide variant
Location: chr20:38509147 (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.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.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-pro271ala (accessed [today's date]).

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