Is SSTR4 p.Ala45Pro (c.133G>C) pathogenic?

SSTR4 p.Ala45Pro (c.133G>C) is classified Uncertain significance in SSTR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.0934); Ultra-rare (popmax 0.0489%, amr).

How common is SSTR4 p.Ala45Pro (c.133G>C) in the general population?

SSTR4 p.Ala45Pro (c.133G>C) is ultra-rare (popmax 0.0489%, amr) (gnomAD).

What do computational predictors say about SSTR4 p.Ala45Pro (c.133G>C)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

SSTR4 p.Ala45Pro

c.133G>C · rs758666610 · VCV3170517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0489%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -14.26	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -3.4, phastCons 0.027
Regional constraint	o/e 1.20	unconstrained · MANE · 1,163 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	14.39	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 0.0489% Admixed American · 24/49,100 alleles

Filtering AF 0.0336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00737% 114/1,545,764 alleles · ultra-rare exomes 94/1,393,692 · genomes 20/152,072 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0489%	2,046
Remaining individualsnot grpmax-eligible	0.0135%	7,424
European (non-Finnish)	0.00704%	14,214
African / African-American	0.00139%	71,782

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: SSTR4
Protein: p.Ala45Pro
Coding: c.133G>C
MANE Select: NM_001052
dbSNP: rs758666610
Type: single nucleotide variant
Location: chr20:23035616 (GRCh38)
Structure: AlphaFold pLDDT 78.72 · 2 PDB

Full SSTR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SSTR4 p.Leu233= Benign ★★ same type
SSTR4 p.Thr17= Benign ★★ same type
SSTR4 p.Val210= Benign ★★ same type
SSTR4 p.Ala155Val Uncertain significance ★ ⚠ same type
SSTR4 p.Ala18Thr Uncertain significance ★ ⚠ same type
SSTR4 p.Ala240Val Uncertain significance ★ ⚠ same type
SSTR4 p.Ala28Ser Uncertain significance ★ ⚠ same type
SSTR4 p.Ala302Gly 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/sstr4-p-ala45pro (accessed [today's date]).

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