Is RALGAPB p.Val880Phe (c.2638G>T) pathogenic?

RALGAPB p.Val880Phe (c.2638G>T) is classified Uncertain significance in RALGAPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.3547); Very rare (popmax 0.005%, amr).

How common is RALGAPB p.Val880Phe (c.2638G>T) in the general population?

RALGAPB p.Val880Phe (c.2638G>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about RALGAPB p.Val880Phe (c.2638G>T)?

AlphaMissense predicts ambiguous (score 0.3547) — an in-silico prediction, not a clinical call.

RALGAPB p.Val880Phe

c.2638G>T · VCV4575521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3547	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -4.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.78, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,992 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,980 alleles · very rare exomes 3/1,461,852 · genomes 1/152,128 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,997
East Asian	0.00223%	44,882

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.Val880Phe
Coding: c.2638G>T
MANE Select: NM_020336
Type: single nucleotide variant
Location: chr20:38541116 (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-val880phe (accessed [today's date]).

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