Is SPTLC2 p.Pro413= (c.1239T>C) pathogenic?

SPTLC2 p.Pro413= (c.1239T>C) is classified Benign/Likely benign in SPTLC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). Rare (popmax 0.132%, mid); Associated with Inborn genetic diseases.

What condition is associated with SPTLC2 p.Pro413= (c.1239T>C)?

SPTLC2 p.Pro413= (c.1239T>C) is associated with Inborn genetic diseases, neuropathy, hereditary sensory and autonomic, type 1C (ClinVar).

How common is SPTLC2 p.Pro413= (c.1239T>C) in the general population?

SPTLC2 p.Pro413= (c.1239T>C) is rare (popmax 0.132%, mid) (gnomAD).

SPTLC2 p.Pro413=

c.1239T>C · rs140041902 · VCV314670

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.086	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.3	GERP -4.5
Overall
CADD	1.835	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0667%

Overall 0.0194% 313/1,614,168 alleles · rare exomes 234/1,461,852 · genomes 79/152,316 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
Admixed American	0.0933%	1,072
African / African-American	0.084%	1,191
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
European (non-Finnish)	0.0122%	8,195
South Asian	0.0022%	45,536

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: SPTLC2
Protein: p.Pro413=
Coding: c.1239T>C
MANE Select: NM_004863
dbSNP: rs140041902
Type: single nucleotide variant
Location: chr14:77552160 (GRCh38)
Gene constraint: LOEUF 0.494 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 86.47 · 17 PDB
Residue 413: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuropathy, hereditary sensory and autonomic, type 1C

Similar variants

SPTLC2 p.Pro413Ser Uncertain significance ★ ⚠ same residue
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

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-pro413 (accessed [today's date]).

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