Is SSTR3 p.Ala264Val (c.791C>T) pathogenic?

SSTR3 p.Ala264Val (c.791C>T) is classified Uncertain significance in SSTR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0939); Very rare (popmax 0.00549%, sas).

How common is SSTR3 p.Ala264Val (c.791C>T) in the general population?

SSTR3 p.Ala264Val (c.791C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about SSTR3 p.Ala264Val (c.791C>T)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

SSTR3 p.Ala264Val

c.791C>T · rs139412786 · VCV2381765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -6.57	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 0.045	GERP -1.6
Regional constraint	o/e 0.83	unconstrained · MANE · 1,253 bp · p 4.2e-05 · 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 0.00549% South Asian · 5/91,074 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00397% 64/1,612,508 alleles · very rare exomes 54/1,460,272 · genomes 10/152,236 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
European (non-Finnish)	0.00475%	21,066
Finnishnot grpmax-eligible	0.00318%	31,454
Admixed American	0.00167%	59,998

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.Ala264Val
Coding: c.791C>T
MANE Select: NM_001051
dbSNP: rs139412786
Type: single nucleotide variant
Location: chr22:37207013 (GRCh38)
Gene constraint: LOEUF 1.881 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 74.90 · 3 PDB
Residue 264: 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.Ala172Val Uncertain significance ★ ⚠ same type
SSTR3 p.Ala200Val 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-ala264val (accessed [today's date]).

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