Is SLC17A5 p.Trp186Ter (c.558G>A) pathogenic?

SLC17A5 p.Trp186Ter (c.558G>A) is classified Likely pathogenic in SLC17A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). Very rare (popmax 0.0011%, sas); Associated with free sialic acid storage disease, infantile form.

What condition is associated with SLC17A5 p.Trp186Ter (c.558G>A)?

SLC17A5 p.Trp186Ter (c.558G>A) is associated with free sialic acid storage disease, infantile form, Salla disease (ClinVar).

How common is SLC17A5 p.Trp186Ter (c.558G>A) in the general population?

SLC17A5 p.Trp186Ter (c.558G>A) is very rare (popmax 0.0011%, sas) (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.Trp186Ter

c.558G>A · VCV3594120

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Overall 0.000124% 2/1,613,850 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	8.48e-05%	1,179,898

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.Trp186Ter
Coding: c.558G>A
MANE Select: NM_012434
Type: single nucleotide variant
Location: chr6:73638467 (GRCh38)
Gene constraint: LOEUF 1.065 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.12 · 7 PDB
Residue 186: an α-helix

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.Trp186Cys 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-trp186ter (accessed [today's date]).

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