Is SSTR4 p.Val266Phe (c.796G>T) pathogenic?

SSTR4 p.Val266Phe (c.796G>T) is classified Uncertain significance in SSTR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.1653); Very rare (popmax 0.00329%, sas).

How common is SSTR4 p.Val266Phe (c.796G>T) in the general population?

SSTR4 p.Val266Phe (c.796G>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about SSTR4 p.Val266Phe (c.796G>T)?

AlphaMissense predicts likely benign (score 0.1653) — an in-silico prediction, not a clinical call.

SSTR4 p.Val266Phe

c.796G>T · VCV3322881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1653	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.58	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 1.4	GERP -3.8, phastCons 0.051
Regional constraint	o/e 1.20	unconstrained · MANE · 1,163 bp · p 3.1e-06 · regional, not allelic
Overall
CADD	22.0	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 0.00329% South Asian · 3/91,088 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,614,160 alleles · very rare exomes 4/1,461,878 · genomes 0/152,282 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,363
East Asian	0.00223%	44,850

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.Val266Phe
Coding: c.796G>T
MANE Select: NM_001052
Type: single nucleotide variant
Location: chr20:23036279 (GRCh38)
Structure: AlphaFold pLDDT 78.72 · 2 PDB
Residue 266: an α-helix

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

Similar variants

SSTR4 p.Val266Ala Likely benign ★ 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-val266phe (accessed [today's date]).

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