Is SNAP29 p.Ala20Pro (c.58G>C) pathogenic?

SNAP29 p.Ala20Pro (c.58G>C) is classified Uncertain significance in SNAP29 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-27). AlphaMissense: likely benign (0.068); Ultra-rare (popmax 0.0824%, mid); Associated with Inborn genetic diseases.

What condition is associated with SNAP29 p.Ala20Pro (c.58G>C)?

SNAP29 p.Ala20Pro (c.58G>C) is associated with Inborn genetic diseases (ClinVar).

How common is SNAP29 p.Ala20Pro (c.58G>C) in the general population?

SNAP29 p.Ala20Pro (c.58G>C) is ultra-rare (popmax 0.0824%, mid) (gnomAD).

What do computational predictors say about SNAP29 p.Ala20Pro (c.58G>C)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

SNAP29 p.Ala20Pro

c.58G>C · rs765170256 · VCV1162875

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.40	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 -0.57
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.086 · regional, not allelic
Overall
CADD	4.08	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 0.0824% Middle Eastern · 5/6,068 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00118% 19/1,604,826 alleles · ultra-rare exomes 17/1,452,618 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0824%	1,214
Admixed American	0.00686%	14,585
Remaining individualsnot grpmax-eligible	0.00161%	62,100
African / African-American	0.00134%	74,894
South Asian	0.00111%	89,726
European (non-Finnish)	0.000595%	168,164

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: SNAP29
Protein: p.Ala20Pro
Coding: c.58G>C
MANE Select: NM_004782
dbSNP: rs765170256
Type: single nucleotide variant
Location: chr22:20859168 (GRCh38)
Gene constraint: LOEUF 0.833 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 75.85 · 2 PDB
Residue 20: the 'disordered' region

Full SNAP29 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

SNAP29 p.Ala20= Likely benign ★ same residue
SNAP29 p.Arg215Cys Uncertain significance ★★ same condition
SNAP29 p.Arg41Lys Uncertain significance ★★ ⚠ same condition
SNAP29 p.Arg83Cys Uncertain significance ★★ ⚠ same condition
SNAP29 p.Arg85Gln Uncertain significance ★★ ⚠ same condition
SNAP29 p.Asn9Ser Uncertain significance ★★ ⚠ same condition
SNAP29 p.Asp17Glu Uncertain significance ★★ ⚠ same condition
SNAP29 p.Asp232Gly 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/snap29-p-ala20pro (accessed [today's date]).

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