Is SLC5A7 p.Ser495Cys (c.1484C>G) pathogenic?

SLC5A7 p.Ser495Cys (c.1484C>G) is classified Uncertain significance in SLC5A7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-10). AlphaMissense: likely pathogenic (0.8414); Very rare (popmax 0.000169%, nfe); Associated with congenital myasthenic syndrome 20.

What condition is associated with SLC5A7 p.Ser495Cys (c.1484C>G)?

SLC5A7 p.Ser495Cys (c.1484C>G) is associated with congenital myasthenic syndrome 20, neuronopathy, distal hereditary motor, type 7A (ClinVar).

How common is SLC5A7 p.Ser495Cys (c.1484C>G) in the general population?

SLC5A7 p.Ser495Cys (c.1484C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about SLC5A7 p.Ser495Cys (c.1484C>G)?

AlphaMissense predicts likely pathogenic (score 0.8414) — an in-silico prediction, not a clinical call.

SLC5A7 p.Ser495Cys

c.1484C>G · rs1446927168 · VCV1426538

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital myasthenic syndrome 20

Computational evidence

Protein change
AlphaMissense	0.8414	likely pathogenic
REVEL	0.93	moderately pathogenic-leaning
SaProt	LLR -11.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 370 bp · p 0.58 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,960 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,882 alleles · very rare exomes 1/1,461,686 · genomes 1/152,196 · 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.Ser495Cys
Coding: c.1484C>G
MANE Select: NM_021815
dbSNP: rs1446927168
Type: single nucleotide variant
Location: chr2:108010602 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 12 PDB
Residue 495: an α-helix

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.Ser495= Likely benign ★ 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-ser495cys (accessed [today's date]).

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