Is SLC16A2 p.Pro41= (c.123C>T) pathogenic?

SLC16A2 p.Pro41= (c.123C>T) is classified Benign/Likely benign in SLC16A2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.45%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC16A2 p.Pro41= (c.123C>T)?

SLC16A2 p.Pro41= (c.123C>T) is associated with Inborn genetic diseases, hereditary spastic paraplegia (ClinVar).

How common is SLC16A2 p.Pro41= (c.123C>T) in the general population?

SLC16A2 p.Pro41= (c.123C>T) is low-frequency (popmax 3.45%, afr) (gnomAD).

SLC16A2 p.Pro41=

c.123C>T · rs369603991 · VCV193348

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.45%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	1.473	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.45% African / African-American · 1,917/55,513 alleles

Filtering AF 3.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.27%

Overall 0.184% 2,104/1,144,911 alleles · low-frequency exomes 1,033/1,033,295 · genomes 1,071/111,616 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.45%	29
Remaining individualsnot grpmax-eligible	0.205%	488
Admixed American	0.164%	610
Middle Eastern	0.124%	805
South Asian	0.00573%	17,452
European (non-Finnish)	0.00268%	37,365

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.Pro41=
Coding: c.123C>T
MANE Select: NM_006517
dbSNP: rs369603991
Type: single nucleotide variant
Location: chrX:74421760 (GRCh38)
Structure: AlphaFold pLDDT 79.48 · 7 PDB
Residue 41: the 'disordered' region

Full SLC16A2 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: hereditary spastic paraplegia

Similar variants

SLC16A2 p.Arg371Cys Pathogenic/Likely pathogenic ★★ same condition
SLC16A2 p.Arg302Cys Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Arg319Cys Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Glu134Gly Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Gly206Asp Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Ile465Thr Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Phe164Leu Uncertain significance ★★ ⚠ same condition
SLC16A2 p.Pro382Leu 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-pro41 (accessed [today's date]).

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