Is SSTR4 p.Arg110Ser (c.328C>A) pathogenic?

SSTR4 p.Arg110Ser (c.328C>A) is classified Uncertain significance in SSTR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.2338); Very rare (popmax 0.00114%, sas).

How common is SSTR4 p.Arg110Ser (c.328C>A) in the general population?

SSTR4 p.Arg110Ser (c.328C>A) is very rare (popmax 0.00114%, sas) (gnomAD).

What do computational predictors say about SSTR4 p.Arg110Ser (c.328C>A)?

AlphaMissense predicts likely benign (score 0.2338) — an in-silico prediction, not a clinical call.

SSTR4 p.Arg110Ser

c.328C>A · VCV3322880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2338	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.53	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 1.3	GERP 0.86, phastCons 0.44
Regional constraint	o/e 1.20	unconstrained · MANE · 1,163 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	15.7	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 0.00114% South Asian · 1/87,740 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.00044% 7/1,590,926 alleles · very rare exomes 5/1,438,606 · genomes 2/152,320 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00114%	87,740
European (non-Finnish)	0.000514%	194,732

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.Arg110Ser
Coding: c.328C>A
MANE Select: NM_001052
Type: single nucleotide variant
Location: chr20:23035811 (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.Arg110His Uncertain significance ★ ⚠ same residue
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

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-arg110ser (accessed [today's date]).

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