Is SLC2A1 p.Pro149Ser (c.445C>T) pathogenic?

SLC2A1 p.Pro149Ser (c.445C>T) is classified Uncertain significance in SLC2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-08). AlphaMissense: likely pathogenic (0.8268); Absent from gnomAD v4.1.

How common is SLC2A1 p.Pro149Ser (c.445C>T) in the general population?

SLC2A1 p.Pro149Ser (c.445C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SLC2A1 p.Pro149Ser (c.445C>T)?

AlphaMissense predicts likely pathogenic (score 0.8268) — an in-silico prediction, not a clinical call.

SLC2A1 p.Pro149Ser

c.445C>T · VCV3371526

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8268 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8268	likely pathogenic
REVEL	0.903	moderately pathogenic-leaning
SaProt	LLR -13.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 114 bp · p 9.7e-09 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: SLC2A1
Protein: p.Pro149Ser
Coding: c.445C>T
MANE Select: NM_006516
Type: single nucleotide variant
Location: chr1:42930697 (GRCh38)
Gene constraint: LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 90.30 · 5 PDB
Residue 149: a UniProt-annotated variant site (in eig12; uncertain significance)

Full SLC2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC2A1 p.Pro149= Likely benign ★ same residue
SLC2A1 c.115-2A>C Pathogenic ★★ same type
SLC2A1 c.115-2A>G Pathogenic ★★ same type
SLC2A1 c.1279-2A>G Likely pathogenic ★★ same type
SLC2A1 c.18+1G>A Pathogenic ★★ same type
SLC2A1 c.19-2A>G Pathogenic ★★ same type
SLC2A1 c.275+1G>C Pathogenic ★★ same type
SLC2A1 c.276-1G>A Pathogenic ★★ 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/slc2a1-p-pro149ser (accessed [today's date]).

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