Is S1PR2 p.Arg297Pro (c.890G>C) pathogenic?

S1PR2 p.Arg297Pro (c.890G>C) is classified Uncertain significance in S1PR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). AlphaMissense: likely pathogenic (0.6144); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with S1PR2 p.Arg297Pro (c.890G>C)?

S1PR2 p.Arg297Pro (c.890G>C) is associated with Inborn genetic diseases (ClinVar).

How common is S1PR2 p.Arg297Pro (c.890G>C) in the general population?

S1PR2 p.Arg297Pro (c.890G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about S1PR2 p.Arg297Pro (c.890G>C)?

AlphaMissense predicts likely pathogenic (score 0.6144) — an in-silico prediction, not a clinical call.

S1PR2 p.Arg297Pro

c.890G>C · rs773635875 · VCV2495745

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6144	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -12.82	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.35, phastCons 0.91
Regional constraint	o/e 0.74	unconstrained · MANE · 1,058 bp · p 8.2e-09 · regional, not allelic
Overall
CADD	20.5	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 0.0011% South Asian · 1/91,066 alleles

Overall 6.2e-05% 1/1,612,368 alleles · very rare exomes 1/1,459,990 · genomes 0/152,378 · joint denominator

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.Arg297Pro
Coding: c.890G>C
MANE Select: NM_004230
dbSNP: rs773635875
Type: single nucleotide variant
Location: chr19:10224016 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

S1PR2 p.Arg297Trp Uncertain significance ★★ ⚠ same residue
S1PR2 p.Ala36Val Uncertain significance ★★ ⚠ same condition
S1PR2 p.Ala77Thr Uncertain significance ★★ ⚠ same condition
S1PR2 p.Arg211His Uncertain significance ★★ ⚠ same condition
S1PR2 p.Arg217His Uncertain significance ★★ ⚠ same condition
S1PR2 p.Arg293Trp Uncertain significance ★★ ⚠ same condition
S1PR2 p.Arg315Gln Uncertain significance ★★ ⚠ same condition
S1PR2 p.Arg329His Uncertain significance ★★ ⚠ 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/s1pr2-p-arg297pro (accessed [today's date]).

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