Is RPS2 p.Arg46= (c.138A>G) pathogenic?

RPS2 p.Arg46= (c.138A>G) is classified Benign in RPS2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-21). Common (popmax 7.61%, afr) — too common for a highly-penetrant pathogenic allele.

RPS2 p.Arg46=

Q: How common is RPS2 p.Arg46= (c.138A>G) in the general population?

RPS2 p.Arg46= (c.138A>G) is common (popmax 7.61%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.138A>G · rs78924165 · VCV768738

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.61%, afr) — too common for a highly-penetrant pathogenic allele

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 -12	GERP -3.8
Overall
CADD	5.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.61% African / African-American · 5,698/74,830 alleles

Filtering AF 7.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.38%

Overall 0.399% 6,414/1,607,308 alleles · common exomes 3,143/1,455,106 · genomes 3,271/152,202 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.61%	13
Remaining individualsnot grpmax-eligible	0.517%	193
Admixed American	0.441%	227
Middle Eastern	0.329%	304
South Asian	0.0154%	6,482
European (non-Finnish)	0.0084%	11,898
Ashkenazi Jewishnot grpmax-eligible	0.00679%	14,719
East Asian	0.00224%	44,642

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: RPS2
Protein: p.Arg46=
Coding: c.138A>G
MANE Select: NM_002952
dbSNP: rs78924165
Type: single nucleotide variant
Location: chr16:1964488 (GRCh38)
Gene constraint: LOEUF 0.493 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 82.10 · 204 PDB
Residue 46: the 'disordered' region

Full RPS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RPS2 p.Ser85= Benign ★★ same type
RPS2 p.Ala198Ser Uncertain significance ★ ⚠ same type
RPS2 p.Ala291Thr Uncertain significance ★ ⚠ same type
RPS2 p.Ala5Gly Uncertain significance ★ ⚠ same type
RPS2 p.Ala8Pro Uncertain significance ★ ⚠ same type
RPS2 p.Ala8Val Uncertain significance ★ ⚠ same type
RPS2 p.Arg167Gly Uncertain significance ★ ⚠ same type
RPS2 p.Arg187His 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/rps2-p-arg46 (accessed [today's date]).

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