Is SPNS2 p.Pro71= (c.213C>T) pathogenic?

SPNS2 p.Pro71= (c.213C>T) is classified Likely benign in SPNS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Very rare (popmax 8.95e-05%, nfe).

How common is SPNS2 p.Pro71= (c.213C>T) in the general population?

SPNS2 p.Pro71= (c.213C>T) is very rare (popmax 8.95e-05%, nfe) (gnomAD).

SPNS2 p.Pro71=

c.213C>T · rs2507684281 · VCV2647256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.95e-05%, 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 0.4	GERP -0.11, phastCons 0.19
Overall
CADD	7.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.95e-05% European (non-Finnish) · 1/1,117,668 alleles

Overall 6.8e-05% 1/1,471,652 alleles · very rare exomes 1/1,320,200 · genomes 0/151,452 · 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: SPNS2
Protein: p.Pro71=
Coding: c.213C>T
MANE Select: NM_001124758
dbSNP: rs2507684281
Type: single nucleotide variant
Location: chr17:4499260 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 18 PDB
Residue 71: the 'disordered' region

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

Similar variants

SPNS2 p.Pro71Ser Uncertain significance ★ ⚠ same residue
SPNS2 p.Pro71Thr Uncertain significance ★ ⚠ same residue
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

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-pro71 (accessed [today's date]).

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