Is SSTR2 p.Ala181Val (c.542C>T) pathogenic?

SSTR2 p.Ala181Val (c.542C>T) is classified Uncertain significance in SSTR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.8527); Absent from gnomAD v4.1.

How common is SSTR2 p.Ala181Val (c.542C>T) in the general population?

SSTR2 p.Ala181Val (c.542C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SSTR2 p.Ala181Val (c.542C>T)?

AlphaMissense predicts likely pathogenic (score 0.8527) — an in-silico prediction, not a clinical call.

SSTR2 p.Ala181Val

c.542C>T · VCV4589999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8527	likely pathogenic
REVEL	0.155	moderately benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 7.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 640 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SSTR2
Protein: p.Ala181Val
Coding: c.542C>T
MANE Select: NM_001050
Type: single nucleotide variant
Location: chr17:73169861 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 81.75 · 17 PDB
Residue 181: a disulfide bond; a β-strand

Full SSTR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SSTR2 p.Arg157Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Arg184Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Arg340Gln Uncertain significance ★ ⚠ same type
SSTR2 p.Asn22Ser Uncertain significance ★ ⚠ same type
SSTR2 p.Asn318Ser Uncertain significance ★ ⚠ same type
SSTR2 p.Asn325Lys Uncertain significance ★ ⚠ same type
SSTR2 p.Asn9Ser Uncertain significance ★ ⚠ same type
SSTR2 p.Asp337His 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/sstr2-p-ala181val (accessed [today's date]).

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