Is SNAP29 p.Pro24= (c.72T>A) pathogenic?

SNAP29 p.Pro24= (c.72T>A) is classified Benign/Likely benign in SNAP29 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-08). Low-frequency (popmax 1.13%, afr); Associated with CEDNIK syndrome.

What condition is associated with SNAP29 p.Pro24= (c.72T>A)?

SNAP29 p.Pro24= (c.72T>A) is associated with CEDNIK syndrome (ClinVar).

How common is SNAP29 p.Pro24= (c.72T>A) in the general population?

SNAP29 p.Pro24= (c.72T>A) is low-frequency (popmax 1.13%, afr) (gnomAD).

How is CEDNIK syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SNAP29 p.Pro24=

c.72T>A · rs149837436 · VCV734948

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, afr)

Conditions

CEDNIK syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4
Overall
CADD	4.345	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.13% African / African-American · 845/74,972 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0596% 956/1,604,154 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.13%	89
Remaining individualsnot grpmax-eligible	0.0853%	1,172
Admixed American	0.0844%	1,184
Middle Eastern	0.0497%	2,014
South Asian	0.00223%	44,837
European (non-Finnish)	0.00034%	294,203

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.Pro24=
Coding: c.72T>A
MANE Select: NM_004782
dbSNP: rs149837436
Type: single nucleotide variant
Location: chr22:20859182 (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 24: the 'disordered' region

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

Disease context

CEDNIK syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For CEDNIK syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SNAP29 p.Pro24Leu Uncertain significance ★ ⚠ same residue
SNAP29 p.Arg85Ter Pathogenic/Likely pathogenic ★★ same condition
SNAP29 p.Met1Thr Pathogenic/Likely pathogenic ★★ same condition
SNAP29 c.-76G>A Uncertain significance ★★ same condition
SNAP29 c.*3014C>T Uncertain significance ★★ same condition
SNAP29 c.*840G>C Uncertain significance ★★ same condition
SNAP29 p.Arg215Cys Uncertain significance ★★ same condition
SNAP29 p.Asp203Asn 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-pro24 (accessed [today's date]).

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