Is SSTR3 p.Ser32Leu (c.95C>T) pathogenic?

SSTR3 p.Ser32Leu (c.95C>T) is classified Uncertain significance in SSTR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.1385); Ultra-rare (popmax 0.011%, afr).

How common is SSTR3 p.Ser32Leu (c.95C>T) in the general population?

SSTR3 p.Ser32Leu (c.95C>T) is ultra-rare (popmax 0.011%, afr) (gnomAD).

What do computational predictors say about SSTR3 p.Ser32Leu (c.95C>T)?

AlphaMissense predicts likely benign (score 0.1385) — an in-silico prediction, not a clinical call.

SSTR3 p.Ser32Leu

c.95C>T · VCV3801870

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1385 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1385	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -10.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 1,253 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.011% African / African-American · 8/72,906 alleles

Filtering AF 0.00541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0039%

Overall 0.00375% 58/1,545,128 alleles · ultra-rare exomes 46/1,392,770 · genomes 12/152,358 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0425%	2,351
African / African-Americangrpmax	0.011%	9,113
East Asian	0.00907%	11,027
Remaining individualsnot grpmax-eligible	0.00842%	11,880
Admixed American	0.00197%	50,640
European (non-Finnish)	0.00122%	81,749

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser32Leu
Coding: c.95C>T
MANE Select: NM_001051
Type: single nucleotide variant
Location: chr22:37207709 (GRCh38)
Gene constraint: LOEUF 1.881 · pLI 0.17 (gnomAD)
Structure: AlphaFold pLDDT 74.90 · 3 PDB

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.Ala264Val 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

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-ser32leu (accessed [today's date]).

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