Is SSTR2 p.Ile87Val (c.259A>G) pathogenic?

SSTR2 p.Ile87Val (c.259A>G) is classified Uncertain significance in SSTR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.0702); Very rare (popmax 0.00167%, amr).

How common is SSTR2 p.Ile87Val (c.259A>G) in the general population?

SSTR2 p.Ile87Val (c.259A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about SSTR2 p.Ile87Val (c.259A>G)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

SSTR2 p.Ile87Val

c.259A>G · rs754769639 · VCV2224105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 6.6, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 153 bp · p 3.7e-07 · regional, not allelic
Overall
CADD	18.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,614,158 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
European (non-Finnish)	0.00144%	69,415

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: SSTR2
Protein: p.Ile87Val
Coding: c.259A>G
MANE Select: NM_001050
dbSNP: rs754769639
Type: single nucleotide variant
Location: chr17:73169578 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 17 PDB
Residue 87: an α-helix

Full SSTR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SSTR2 p.Ile87= Likely benign ★ same residue
SSTR2 p.Ala181Val Uncertain significance ★ ⚠ same type
SSTR2 p.Arg157Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Arg184Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Arg340Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Asn22Ser Uncertain significance ★ ⚠ same type
SSTR2 p.Asn318Ser Uncertain significance ★ ⚠ same type
SSTR2 p.Asn325Lys 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/sstr2-p-ile87val (accessed [today's date]).

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