Is SLC5A7 p.Pro419= (c.1257C>T) pathogenic?

SLC5A7 p.Pro419= (c.1257C>T) is classified Likely benign in SLC5A7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). Very rare (popmax 0.00167%, amr); Associated with neuronopathy, distal hereditary motor, type 7A.

How common is SLC5A7 p.Pro419= (c.1257C>T) in the general population?

SLC5A7 p.Pro419= (c.1257C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Distal hereditary motor neuropathy type 7 inherited?

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

SLC5A7 p.Pro419=

Q: What condition is associated with SLC5A7 p.Pro419= (c.1257C>T)?

SLC5A7 p.Pro419= (c.1257C>T) is associated with neuronopathy, distal hereditary motor, type 7A, congenital myasthenic syndrome 20 (ClinVar).

c.1257C>T · rs557717267 · VCV1551194

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

neuronopathy, distal hereditary motor, type 7A

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>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.1	GERP -4.2
Overall
CADD	0.617	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,962 alleles

Overall 6.2e-05% 1/1,613,960 alleles · very rare exomes 0/1,461,738 · genomes 1/152,222 · 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.Pro419=
Coding: c.1257C>T
MANE Select: NM_021815
dbSNP: rs557717267
Type: single nucleotide variant
Location: chr2:108010375 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 12 PDB
Residue 419: an α-helix

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

Disease context

neuronopathy, distal hereditary motor, type 7A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 20

For Distal hereditary motor neuropathy type 7 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

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
SLC5A7 p.Ala222Val 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-pro419 (accessed [today's date]).

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