Is SNAP29 p.Ala65Pro (c.193G>C) pathogenic?

SNAP29 p.Ala65Pro (c.193G>C) is classified Uncertain significance in SNAP29 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-31). AlphaMissense: likely pathogenic (0.7001); Ultra-rare (popmax 0.0417%, amr).

How common is SNAP29 p.Ala65Pro (c.193G>C) in the general population?

SNAP29 p.Ala65Pro (c.193G>C) is ultra-rare (popmax 0.0417%, amr) (gnomAD).

What do computational predictors say about SNAP29 p.Ala65Pro (c.193G>C)?

AlphaMissense predicts likely pathogenic (score 0.7001) — an in-silico prediction, not a clinical call.

SNAP29 p.Ala65Pro

c.193G>C · rs760243787 · VCV448435

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0417%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7001	likely pathogenic
REVEL	0.245	benign-leaning
SaProt	LLR -10.94	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.086 · regional, not allelic
Overall
CADD	18.09	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 0.0417% Admixed American · 25/59,990 alleles

Filtering AF 0.0289% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00161% 26/1,613,124 alleles · ultra-rare exomes 26/1,460,794 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0417%	2,400
European (non-Finnish)	8.48e-05%	1,179,934

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.Ala65Pro
Coding: c.193G>C
MANE Select: NM_004782
dbSNP: rs760243787
Type: single nucleotide variant
Location: chr22:20859303 (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 65: an α-helix

Full SNAP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SNAP29 p.Ala65Thr Uncertain significance ⚠ same residue
SNAP29 p.Arg85Ter Pathogenic/Likely pathogenic ★★ same type
SNAP29 p.Met1Thr Pathogenic/Likely pathogenic ★★ same type
SNAP29 c.-76G>A Uncertain significance ★★ same type
SNAP29 c.*3014C>T Uncertain significance ★★ same type
SNAP29 c.*840G>C Uncertain significance ★★ same type
SNAP29 p.Ala20Pro Uncertain significance ★★ ⚠ same type
SNAP29 p.Arg215Cys 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/snap29-p-ala65pro (accessed [today's date]).

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