Is SPTLC2 p.Phe381= (c.1143T>C) pathogenic?

SPTLC2 p.Phe381= (c.1143T>C) is classified Likely benign in SPTLC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-01). Absent from gnomAD v4.1; Associated with neuropathy, hereditary sensory and autonomic, type 1C.

What condition is associated with SPTLC2 p.Phe381= (c.1143T>C)?

SPTLC2 p.Phe381= (c.1143T>C) is associated with neuropathy, hereditary sensory and autonomic, type 1C (ClinVar).

How common is SPTLC2 p.Phe381= (c.1143T>C) in the general population?

SPTLC2 p.Phe381= (c.1143T>C) is absent from gnomAD v4.1 (gnomAD).

SPTLC2 p.Phe381=

Q: How is Hereditary sensory and autonomic neuropathy type 1 inherited?

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

c.1143T>C · rs2140020443 · VCV1138958

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neuropathy, hereditary sensory and autonomic, type 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.094	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.007	GERP -4.5, phastCons 0.032
Overall
CADD	7.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SPTLC2
Protein: p.Phe381=
Coding: c.1143T>C
MANE Select: NM_004863
dbSNP: rs2140020443
Type: single nucleotide variant
Location: chr14:77555333 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.47 · 17 PDB
Residue 381: a turn

Full SPTLC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary sensory and autonomic, type 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory and autonomic neuropathy type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

SPTLC2 p.Arg183Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
SPTLC2 p.Gly382Val Pathogenic/Likely pathogenic ★★ same condition
SPTLC2 p.Ser384Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
SPTLC2 c.1176+6C>T Uncertain significance ★★ same condition
SPTLC2 c.756+3A>G Uncertain significance ★★ same condition
SPTLC2 c.-160A>G Uncertain significance ★★ same condition
SPTLC2 c.*100G>A Uncertain significance ★★ same condition
SPTLC2 p.Ala231Thr 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/sptlc2-p-phe381 (accessed [today's date]).

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