Is S1PR3 p.Arg306Gln (c.917G>A) pathogenic?

S1PR3 p.Arg306Gln (c.917G>A) is classified Uncertain significance in S1PR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: ambiguous (0.3545); Very rare (popmax 0.00446%, eas).

How common is S1PR3 p.Arg306Gln (c.917G>A) in the general population?

S1PR3 p.Arg306Gln (c.917G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about S1PR3 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts ambiguous (score 0.3545) — an in-silico prediction, not a clinical call.

S1PR3 p.Arg306Gln

c.917G>A · VCV4158608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Computational evidence

Protein change
AlphaMissense	0.3545	ambiguous
REVEL	0.562	indeterminate
SaProt	LLR -10.08	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,133 bp · p 0.021 · regional, not allelic
Overall
CADD	31.0	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 0.00446% East Asian · 2/44,840 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00105% 17/1,613,708 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,420
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.0011%	90,772
South Asian	0.0011%	91,086

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: S1PR3
Protein: p.Arg306Gln
Coding: c.917G>A
MANE Select: NM_005226
Type: single nucleotide variant
Location: chr9:89002117 (GRCh38)
Gene constraint: LOEUF 1.267 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.81 · 9 PDB
Residue 306: an α-helix

Full S1PR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

S1PR3 c.-148+196C>T Uncertain significance ★ ⚠ same type
S1PR3 c.-148+289A>G Uncertain significance ★ ⚠ same type
S1PR3 c.-226G>A Uncertain significance ★ ⚠ same type
S1PR3 p.Ala230Val Uncertain significance ★ ⚠ same type
S1PR3 p.Ala254Thr Uncertain significance ★ ⚠ same type
S1PR3 p.Ala292Thr Uncertain significance ★ same type
S1PR3 p.Arg136Gln Uncertain significance ★ ⚠ same type
S1PR3 p.Arg13Leu 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/s1pr3-p-arg306gln (accessed [today's date]).

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