Is SSTR5 p.Leu196Pro (c.587T>C) pathogenic?

SSTR5 p.Leu196Pro (c.587T>C) is classified Uncertain significance in SSTR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1288); Ultra-rare (popmax 0.0152%, amr).

How common is SSTR5 p.Leu196Pro (c.587T>C) in the general population?

SSTR5 p.Leu196Pro (c.587T>C) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

What do computational predictors say about SSTR5 p.Leu196Pro (c.587T>C)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

SSTR5 p.Leu196Pro

c.587T>C · VCV3322884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -9.42	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 2.8	GERP -3.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,091 bp · p 0.24 · regional, not allelic
Overall
CADD	22.7	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 0.0152% Admixed American · 9/59,402 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00584%

Overall 0.00361% 58/1,608,082 alleles · ultra-rare exomes 56/1,455,970 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0152%	6,600
African / African-American	0.00401%	24,927
European (non-Finnish)	0.00365%	27,390
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,392
Remaining individualsnot grpmax-eligible	0.00321%	31,114

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: SSTR5
Protein: p.Leu196Pro
Coding: c.587T>C
MANE Select: NM_001172560
Type: single nucleotide variant
Location: chr16:1079455 (GRCh38)
Gene constraint: LOEUF 1.931 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 81.91 · 7 PDB
Residue 196: an α-helix

Full SSTR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SSTR5 p.Leu196= Likely benign ★ same residue
SSTR5 p.Thr98Met Uncertain significance ★★ ⚠ same type
SSTR5 p.Ala161= Benign ★★ same type
SSTR5 p.Ala231= Benign/Likely benign ★★ same type
SSTR5 p.Arg240Trp Benign/Likely benign ★★ same type
SSTR5 p.Leu219= Benign ★★ same type
SSTR5 p.Leu48Met Benign ★★ same type
SSTR5 p.Phe107= Benign ★★ 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/sstr5-p-leu196pro (accessed [today's date]).

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