Is SLC17A5 p.Pro191= (c.573C>G) pathogenic?

SLC17A5 p.Pro191= (c.573C>G) is classified Conflicting classifications of pathogenicity in SLC17A5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-11-07). Very rare (popmax 0.00314%, nfe); Associated with free sialic acid storage disease, infantile form.

What condition is associated with SLC17A5 p.Pro191= (c.573C>G)?

SLC17A5 p.Pro191= (c.573C>G) is associated with free sialic acid storage disease, infantile form, Salla disease (ClinVar).

How common is SLC17A5 p.Pro191= (c.573C>G) in the general population?

SLC17A5 p.Pro191= (c.573C>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

How is Free sialic acid storage disease inherited?

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

SLC17A5 p.Pro191=

c.573C>G · rs924683894 · VCV911669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

free sialic acid storage disease, infantile form

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 0.39	GERP -4.8, phastCons 0.98
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,968 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00229% 37/1,613,938 alleles · very rare

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: SLC17A5
Protein: p.Pro191=
Coding: c.573C>G
MANE Select: NM_012434
dbSNP: rs924683894
Type: single nucleotide variant
Location: chr6:73638452 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 7 PDB

Full SLC17A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

free sialic acid storage disease, infantile form — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Salla disease

For Free sialic acid storage disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

SLC17A5 p.Pro191His Uncertain significance ⚠ same residue
SLC17A5 c.1111+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC17A5 c.1111+1G>T Likely pathogenic ★★ same condition
SLC17A5 c.1259+1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC17A5 c.1259+2T>C Pathogenic ★★ same condition
SLC17A5 c.1260-2A>C Pathogenic/Likely pathogenic ★★ same condition
SLC17A5 c.613+1G>A Likely pathogenic ★★ same condition
SLC17A5 c.700+2T>C Likely pathogenic ★★ 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/slc17a5-p-pro191 (accessed [today's date]).

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