Is SLC13A5 p.Pro487= (c.1461G>T) pathogenic?

SLC13A5 p.Pro487= (c.1461G>T) is classified Likely benign in SLC13A5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). Very rare (popmax 0.00171%, amr); Associated with developmental and epileptic encephalopathy, 25.

What condition is associated with SLC13A5 p.Pro487= (c.1461G>T)?

SLC13A5 p.Pro487= (c.1461G>T) is associated with developmental and epileptic encephalopathy, 25 (ClinVar).

How common is SLC13A5 p.Pro487= (c.1461G>T) in the general population?

SLC13A5 p.Pro487= (c.1461G>T) is very rare (popmax 0.00171%, amr) (gnomAD).

SLC13A5 p.Pro487=

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

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

c.1461G>T · VCV3673895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Conditions

developmental and epileptic encephalopathy, 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.2	GERP -3.9
Overall
CADD	1.38	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00171% Admixed American · 1/58,350 alleles

Overall 6.22e-05% 1/1,606,698 alleles · very rare exomes 1/1,454,418 · genomes 0/152,280 · joint denominator

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: SLC13A5
Protein: p.Pro487=
Coding: c.1461G>T
MANE Select: NM_177550
Type: single nucleotide variant
Location: chr17:6687643 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.70 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.97 · 7 PDB
Residue 487: a UniProt-annotated variant site (in dee25; loss of localization to plasma membrane; loss of function in citrate transport); an α-helix

Full SLC13A5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

SLC13A5 p.Pro487Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SLC13A5 c.1276-1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC13A5 c.548-1G>A Likely pathogenic ★★ same condition
SLC13A5 c.548-2A>G Likely pathogenic ★★ same condition
SLC13A5 p.Arg333Ter Pathogenic/Likely pathogenic ★★ same condition
SLC13A5 p.Gly219Arg Pathogenic/Likely pathogenic ★★ same condition
SLC13A5 p.Leu488Pro Likely pathogenic ★★ same condition
SLC13A5 p.Ser427Leu Pathogenic/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/slc13a5-p-pro487 (accessed [today's date]).

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