Is SPNS2 p.Arg342= (c.1026C>T) pathogenic?

SPNS2 p.Arg342= (c.1026C>T) is classified Likely benign in SPNS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-01). Rare (popmax 0.416%, nfe).

How common is SPNS2 p.Arg342= (c.1026C>T) in the general population?

SPNS2 p.Arg342= (c.1026C>T) is rare (popmax 0.416%, nfe) (gnomAD).

SPNS2 p.Arg342=

c.1026C>T · rs182141708 · VCV2570967

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.416%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	0.043	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.416% European (non-Finnish) · 4,906/1,179,938 alleles

Filtering AF 0.406% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.332% 5,354/1,613,314 alleles · rare exomes 4,990/1,460,998 · genomes 364/152,316 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.521%	192
European (non-Finnish)grpmax	0.416%	241
Remaining individualsnot grpmax-eligible	0.219%	456
Admixed American	0.0933%	1,072
Finnishnot grpmax-eligible	0.0742%	1,347
African / African-American	0.0666%	1,501
Middle Eastern	0.0165%	6,060
East Asian	0.00223%	44,882
South Asian	0.0022%	45,537

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SPNS2
Protein: p.Arg342=
Coding: c.1026C>T
MANE Select: NM_001124758
dbSNP: rs182141708
Type: single nucleotide variant
Location: chr17:4533067 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 18 PDB
Residue 342: an α-helix

Full SPNS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SPNS2 p.Ala401Thr Uncertain significance ★★ ⚠ same type
SPNS2 p.Ala545Thr Uncertain significance ★★ ⚠ same type
SPNS2 c.1279-152G>A Benign ★★ same type
SPNS2 c.1344+66C>T Benign ★★ same type
SPNS2 c.1345-58A>G Benign ★★ same type
SPNS2 c.1345-89G>A Benign ★★ same type
SPNS2 c.1443+27C>A Benign ★★ same type
SPNS2 c.1443+28A>G Benign ★★ same type

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/spns2-p-arg342 (accessed [today's date]).

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