Is SSTR3 p.Ala172Val (c.515C>T) pathogenic?

SSTR3 p.Ala172Val (c.515C>T) is classified Uncertain significance in SSTR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0112%, eas).

How common is SSTR3 p.Ala172Val (c.515C>T) in the general population?

SSTR3 p.Ala172Val (c.515C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about SSTR3 p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

SSTR3 p.Ala172Val

c.515C>T · rs759921363 · VCV3170515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -6.27	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 9.9	GERP 0.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 1,253 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	23.2	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 0.0112% East Asian · 5/44,638 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.000347% 5/1,440,530 alleles · ultra-rare

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: SSTR3
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_001051
dbSNP: rs759921363
Type: single nucleotide variant
Location: chr22:37207289 (GRCh38)
Gene constraint: LOEUF 1.881 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 74.90 · 3 PDB
Residue 172: a disulfide bond; an α-helix

Full SSTR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SSTR3 p.Ala157Pro Uncertain significance ★ ⚠ same type
SSTR3 p.Ala170Val Uncertain significance ★ ⚠ same type
SSTR3 p.Ala200Val Uncertain significance ★ ⚠ same type
SSTR3 p.Ala264Val Uncertain significance ★ ⚠ same type
SSTR3 p.Ala74Asp Uncertain significance ★ ⚠ same type
SSTR3 p.Arg150Cys Uncertain significance ★ ⚠ same type
SSTR3 p.Arg153Cys Uncertain significance ★ ⚠ same type
SSTR3 p.Arg155His 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/sstr3-p-ala172val (accessed [today's date]).

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