Is SLC25A46 p.Ser32= (c.96C>T) pathogenic?

SLC25A46 p.Ser32= (c.96C>T) is classified Likely benign in SLC25A46 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-21). Ultra-rare (popmax 0.0233%, sas); Associated with neuropathy, hereditary motor and sensory, type 6B.

What condition is associated with SLC25A46 p.Ser32= (c.96C>T)?

SLC25A46 p.Ser32= (c.96C>T) is associated with neuropathy, hereditary motor and sensory, type 6B (ClinVar).

How common is SLC25A46 p.Ser32= (c.96C>T) in the general population?

SLC25A46 p.Ser32= (c.96C>T) is ultra-rare (popmax 0.0233%, sas) (gnomAD).

How is Hereditary motor and sensory neuropathy type 6 inherited?

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

SLC25A46 p.Ser32=

c.96C>T · rs767703868 · VCV2887554

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, sas)

Conditions

neuropathy, hereditary motor and sensory, type 6B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.063	GERP -1.8, phastCons 0.69
Overall
CADD	10.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0233% South Asian · 20/85,696 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00178% 28/1,571,652 alleles · ultra-rare exomes 26/1,419,428 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0233%	4,285
East Asian	0.007%	14,287
Remaining individualsnot grpmax-eligible	0.00328%	30,449
African / African-American	0.00135%	74,218
European (non-Finnish)	0.000173%	579,462

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: SLC25A46
Protein: p.Ser32=
Coding: c.96C>T
MANE Select: NM_138773
dbSNP: rs767703868
Type: single nucleotide variant
Location: chr5:110739215 (GRCh38)
Gene constraint: LOEUF 1.375 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 1 PDB
Residue 32: a modified residue (phosphoserine); a UniProt-annotated variant site (in pch1e)

Full SLC25A46 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary motor and sensory, type 6B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary motor and sensory neuropathy type 6 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

SLC25A46 c.620+1G>C Likely pathogenic ★★ same condition
SLC25A46 p.Arg340Cys Pathogenic/Likely pathogenic ★★ same condition
SLC25A46 p.Gly102Ter Pathogenic/Likely pathogenic ★★ same condition
SLC25A46 p.Trp160Ter Likely pathogenic ★★ same condition
SLC25A46 c.326+6G>A Uncertain significance ★★ same condition
SLC25A46 p.Ala108Val Uncertain significance ★★ ⚠ same condition
SLC25A46 p.Arg124Cys Uncertain significance ★★ ⚠ same condition
SLC25A46 p.Arg124His 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/slc25a46-p-ser32 (accessed [today's date]).

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