Is SLC16A2 p.Phe246= (c.738C>T) pathogenic?

SLC16A2 p.Phe246= (c.738C>T) is classified Likely benign in SLC16A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with SLC16A2 p.Phe246= (c.738C>T)?

SLC16A2 p.Phe246= (c.738C>T) is associated with Spastic paraplegia (ClinVar).

How common is SLC16A2 p.Phe246= (c.738C>T) in the general population?

SLC16A2 p.Phe246= (c.738C>T) is absent from gnomAD v4.1 (gnomAD).

SLC16A2 p.Phe246=

c.738C>T · rs2519806631 · VCV2103250

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.85	phastCons 1
Overall
CADD	10.09	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: SLC16A2
Protein: p.Phe246=
Coding: c.738C>T
MANE Select: NM_006517
dbSNP: rs2519806631
Type: single nucleotide variant
Location: chrX:74524521 (GRCh38)
Structure: AlphaFold pLDDT 79.48 · 7 PDB
Residue 246: an α-helix

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-phe246 (accessed [today's date]).

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