Is S1PR2 p.Pro302= (c.906G>A) pathogenic?

S1PR2 p.Pro302= (c.906G>A) is classified Likely benign in S1PR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-22). Ultra-rare (popmax 0.0187%, sas).

How common is S1PR2 p.Pro302= (c.906G>A) in the general population?

S1PR2 p.Pro302= (c.906G>A) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

S1PR2 p.Pro302=

c.906G>A · VCV3624283

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

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 -12
Overall
CADD	0.301	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,006 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00977%

Overall 0.00168% 27/1,611,372 alleles · ultra-rare exomes 24/1,459,154 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,353
African / African-American	0.00668%	14,976
Admixed American	0.00334%	29,960
Remaining individualsnot grpmax-eligible	0.00321%	31,184
European (non-Finnish)	8.48e-05%	1,178,688

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.Pro302=
Coding: c.906G>A
MANE Select: NM_004230
Type: single nucleotide variant
Location: chr19:10224000 (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.Pro302Leu Uncertain significance ★ ⚠ same residue
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

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-pro302 (accessed [today's date]).

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