Is SSTR2 p.Val145Ile (c.433G>A) pathogenic?

SSTR2 p.Val145Ile (c.433G>A) is classified Uncertain significance in SSTR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: ambiguous (0.455); Very rare (popmax 0.00136%, nfe).

How common is SSTR2 p.Val145Ile (c.433G>A) in the general population?

SSTR2 p.Val145Ile (c.433G>A) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about SSTR2 p.Val145Ile (c.433G>A)?

AlphaMissense predicts ambiguous (score 0.455) — an in-silico prediction, not a clinical call.

SSTR2 p.Val145Ile

c.433G>A · rs2061227529 · VCV2492201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.455 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Computational evidence

Protein change
AlphaMissense	0.455	ambiguous
REVEL	0.34	indeterminate
SaProt	LLR -8.56	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 7.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 640 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	27.2	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 0.00136% European (non-Finnish) · 16/1,180,054 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000991% 16/1,614,070 alleles · very rare exomes 15/1,461,892 · genomes 1/152,178 · 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: SSTR2
Protein: p.Val145Ile
Coding: c.433G>A
MANE Select: NM_001050
dbSNP: rs2061227529
Type: single nucleotide variant
Location: chr17:73169752 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 17 PDB
Residue 145: an α-helix

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

Similar variants

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
SSTR2 p.Asn9Ser 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-val145ile (accessed [today's date]).

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