Is S1PR2 p.Arg99= (c.297G>A) pathogenic?

S1PR2 p.Arg99= (c.297G>A) is classified Likely benign in S1PR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-19). Ultra-rare (popmax 0.0134%, eas).

How common is S1PR2 p.Arg99= (c.297G>A) in the general population?

S1PR2 p.Arg99= (c.297G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

S1PR2 p.Arg99=

c.297G>A · rs761534939 · VCV1216964

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.93	GERP -5.1
Overall
CADD	1.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,904 alleles

Filtering AF 0.00578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00124% 20/1,613,914 alleles · ultra-rare exomes 17/1,461,634 · genomes 3/152,280 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0208%	4,807
East Asiangrpmax	0.0134%	7,484
Admixed American	0.00167%	60,010

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: S1PR2
Protein: p.Arg99=
Coding: c.297G>A
MANE Select: NM_004230
dbSNP: rs761534939
Type: single nucleotide variant
Location: chr19:10224609 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 82.73 · 2 PDB

Full S1PR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

S1PR2 p.Ala36Val Uncertain significance ★★ ⚠ same type
S1PR2 p.Ala77Thr Uncertain significance ★★ ⚠ same type
S1PR2 p.Ala77Val Uncertain significance ★★ ⚠ same type
S1PR2 p.Arg211His Uncertain significance ★★ ⚠ same type
S1PR2 p.Arg217His Uncertain significance ★★ ⚠ same type
S1PR2 p.Arg293Trp Uncertain significance ★★ ⚠ same type
S1PR2 p.Arg297Trp Uncertain significance ★★ ⚠ same type
S1PR2 p.Arg315Gln 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/s1pr2-p-arg99 (accessed [today's date]).

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