Is SLC16A2 p.Val296= (c.888C>T) pathogenic?

SLC16A2 p.Val296= (c.888C>T) is classified Benign in SLC16A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Ultra-rare (popmax 0.0599%, sas); Associated with Spastic paraplegia.

What condition is associated with SLC16A2 p.Val296= (c.888C>T)?

SLC16A2 p.Val296= (c.888C>T) is associated with Spastic paraplegia (ClinVar).

How common is SLC16A2 p.Val296= (c.888C>T) in the general population?

SLC16A2 p.Val296= (c.888C>T) is ultra-rare (popmax 0.0599%, sas) (gnomAD).

SLC16A2 p.Val296=

c.888C>T · rs763909787 · VCV2151311

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0599%, sas)

Conditions

Spastic paraplegia

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 0.83	phastCons 1
Overall
CADD	6.588	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0599% South Asian · 34/56,793 alleles

Filtering AF 0.044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.00364% 44/1,210,114 alleles · ultra-rare exomes 40/1,098,219 · genomes 4/111,895 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0599%	1,670
Remaining individualsnot grpmax-eligible	0.0021%	47,612
European (non-Finnish)	0.00101%	99,481

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: SLC16A2
Protein: p.Val296=
Coding: c.888C>T
MANE Select: NM_006517
dbSNP: rs763909787
Type: single nucleotide variant
Location: chrX:74524671 (GRCh38)
Structure: AlphaFold pLDDT 79.48 · 7 PDB

Full SLC16A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Spastic paraplegia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC16A2 c.1399+1G>A Pathogenic ★★ same condition
SLC16A2 c.576-1G>A Pathogenic/Likely pathogenic ★★ same condition
SLC16A2 p.Arg171Ter Pathogenic ★★ same condition
SLC16A2 p.Gln16Ter Pathogenic ★★ same condition
SLC16A2 p.Gln52Ter Pathogenic ★★ same condition
SLC16A2 p.Gly327Arg Pathogenic/Likely pathogenic ★★ same condition
SLC16A2 p.Asn471Lys Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Asp521Glu 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/slc16a2-p-val296 (accessed [today's date]).

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