Is SLC5A7 p.Pro463= (c.1389T>C) pathogenic?

SLC5A7 p.Pro463= (c.1389T>C) is classified Likely benign in SLC5A7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). Very rare (popmax 0.00119%, nfe); Associated with congenital myasthenic syndrome 20.

What condition is associated with SLC5A7 p.Pro463= (c.1389T>C)?

SLC5A7 p.Pro463= (c.1389T>C) is associated with congenital myasthenic syndrome 20, neuronopathy, distal hereditary motor, type 7A (ClinVar).

How common is SLC5A7 p.Pro463= (c.1389T>C) in the general population?

SLC5A7 p.Pro463= (c.1389T>C) is very rare (popmax 0.00119%, nfe) (gnomAD).

SLC5A7 p.Pro463=

c.1389T>C · rs1194099959 · VCV1998733

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Conditions

congenital myasthenic syndrome 20

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -2.1, phastCons 0.004
Overall
CADD	6.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,924 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000867% 14/1,613,874 alleles · very rare exomes 13/1,461,692 · genomes 1/152,182 · 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: SLC5A7
Protein: p.Pro463=
Coding: c.1389T>C
MANE Select: NM_021815
dbSNP: rs1194099959
Type: single nucleotide variant
Location: chr2:108010507 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 12 PDB

Full SLC5A7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 20 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronopathy, distal hereditary motor, type 7A

Similar variants

SLC5A7 p.Pro463Ser Uncertain significance ★ ⚠ same residue
SLC5A7 c.895+1G>C Likely pathogenic ★★ same condition
SLC5A7 c.178+4C>G Uncertain significance ★★ same condition
SLC5A7 c.178+6T>C Uncertain significance ★★ same condition
SLC5A7 c.293-10T>C Uncertain significance ★★ same condition
SLC5A7 c.895+4A>G Uncertain significance ★★ same condition
SLC5A7 p.Ala134Val Uncertain significance ★★ ⚠ same condition
SLC5A7 p.Ala143Thr 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/slc5a7-p-pro463 (accessed [today's date]).

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