Is RALGAPB p.Val183Ala (c.548T>C) pathogenic?

RALGAPB p.Val183Ala (c.548T>C) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely benign (0.122); Very rare (popmax 0.00184%, amr).

How common is RALGAPB p.Val183Ala (c.548T>C) in the general population?

RALGAPB p.Val183Ala (c.548T>C) is very rare (popmax 0.00184%, amr) (gnomAD).

What do computational predictors say about RALGAPB p.Val183Ala (c.548T>C)?

AlphaMissense predicts likely benign (score 0.122) — an in-silico prediction, not a clinical call.

RALGAPB p.Val183Ala

c.548T>C · VCV3430085

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00184%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.122	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 4.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 63 kb · p 1.7e-18 · regional, not allelic
Overall
CADD	22.3	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 0.00184% Admixed American · 1/54,392 alleles

Overall 0.000125% 2/1,594,198 alleles · very rare exomes 2/1,441,908 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00184%	54,392
European (non-Finnish)	8.51e-05%	1,174,750

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.Val183Ala
Coding: c.548T>C
MANE Select: NM_020336
Type: single nucleotide variant
Location: chr20:38497511 (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.Val183Ile Uncertain significance ★ ⚠ same residue
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

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-val183ala (accessed [today's date]).

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