Is STX11 p.Pro20Ser (c.58C>T) pathogenic?

STX11 p.Pro20Ser (c.58C>T) is classified Uncertain significance in STX11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-11). AlphaMissense: likely benign (0.0805); Very rare (popmax 0.00659%, sas); Associated with Inborn genetic diseases.

What condition is associated with STX11 p.Pro20Ser (c.58C>T)?

STX11 p.Pro20Ser (c.58C>T) is associated with Inborn genetic diseases (ClinVar).

How common is STX11 p.Pro20Ser (c.58C>T) in the general population?

STX11 p.Pro20Ser (c.58C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about STX11 p.Pro20Ser (c.58C>T)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

STX11 p.Pro20Ser

c.58C>T · rs770639837 · VCV2363849

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -5.67	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 0.25	GERP -0.21, phastCons 0.007
Regional constraint	o/e 1.08	unconstrained · MANE · 860 bp · p 0.11 · regional, not allelic
Overall
CADD	8.816	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 0.00659% South Asian · 6/91,086 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000434% 7/1,614,072 alleles · very rare exomes 6/1,461,856 · genomes 1/152,216 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,181
Admixed American	0.00167%	60,008

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: STX11
Protein: p.Pro20Ser
Coding: c.58C>T
MANE Select: NM_003764
dbSNP: rs770639837
Type: single nucleotide variant
Location: chr6:144186685 (GRCh38)
Gene constraint: LOEUF 1.502 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.08
Residue 20: the 'mediates interaction with stxbp2' region

Full STX11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STX11 p.Arg4Gln Uncertain significance ★★ same condition
STX11 p.Arg4Leu Uncertain significance ★★ ⚠ same condition
STX11 p.Asp145His Uncertain significance ★★ ⚠ same condition
STX11 p.Asp145Tyr Uncertain significance ★★ ⚠ same condition
STX11 p.Asp196His Uncertain significance ★★ ⚠ same condition
STX11 p.Asp23Asn Uncertain significance ★★ ⚠ same condition
STX11 p.Gln131Arg Uncertain significance ★★ ⚠ same condition
STX11 p.His144Gln Uncertain significance ★★ ⚠ same condition

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/stx11-p-pro20ser (accessed [today's date]).

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