Is SSTR4 p.Gln367Pro (c.1100A>C) pathogenic?

SSTR4 p.Gln367Pro (c.1100A>C) is classified Uncertain significance in SSTR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0616); Ultra-rare (popmax 0.0502%, nfe).

How common is SSTR4 p.Gln367Pro (c.1100A>C) in the general population?

SSTR4 p.Gln367Pro (c.1100A>C) is ultra-rare (popmax 0.0502%, nfe) (gnomAD).

What do computational predictors say about SSTR4 p.Gln367Pro (c.1100A>C)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

SSTR4 p.Gln367Pro

c.1100A>C · VCV3449890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0502%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -4.11	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 1.2	GERP -2.3, phastCons 0.98
Regional constraint	o/e 1.20	unconstrained · MANE · 1,163 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	11.2	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 0.0502% European (non-Finnish) · 588/1,172,370 alleles

Filtering AF 0.0467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0454%

Overall 0.038% 607/1,597,472 alleles · ultra-rare exomes 559/1,445,228 · genomes 48/152,244 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0502%	1,994
Remaining individualsnot grpmax-eligible	0.013%	7,718
African / African-American	0.0107%	9,319
Admixed American	0.00519%	19,279

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.Gln367Pro
Coding: c.1100A>C
MANE Select: NM_001052
Type: single nucleotide variant
Location: chr20:23036583 (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-gln367pro (accessed [today's date]).

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