Is RALGAPB p.Ser1453= (c.4359T>C) pathogenic?

RALGAPB p.Ser1453= (c.4359T>C) is classified Benign in RALGAPB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-16). Low-frequency (popmax 1.93%, eas); Associated with RALGAPB-related disorder.

What condition is associated with RALGAPB p.Ser1453= (c.4359T>C)?

RALGAPB p.Ser1453= (c.4359T>C) is associated with RALGAPB-related disorder (ClinVar).

How common is RALGAPB p.Ser1453= (c.4359T>C) in the general population?

RALGAPB p.Ser1453= (c.4359T>C) is low-frequency (popmax 1.93%, eas) (gnomAD).

RALGAPB p.Ser1453=

c.4359T>C · rs138886522 · VCV3033737

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.93%, eas)

Conditions

RALGAPB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP -3.9, phastCons 0.005
Overall
CADD	4.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.93% East Asian · 865/44,860 alleles

Filtering AF 1.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 0.0568% 917/1,613,342 alleles · low-frequency exomes 776/1,461,556 · genomes 141/151,786 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.93%	52
Remaining individualsnot grpmax-eligible	0.0656%	1,524
South Asian	0.00659%	15,174
Admixed American	0.00334%	29,979
European (non-Finnish)	0.000254%	393,210

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.Ser1453=
Coding: c.4359T>C
MANE Select: NM_020336
dbSNP: rs138886522
Type: single nucleotide variant
Location: chr20:38574841 (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.Pro271Ala Uncertain significance ★ ⚠ same condition
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

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-ser1453 (accessed [today's date]).

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