Is SLC2A9 p.Pro103Ala (c.307C>G) pathogenic?

SLC2A9 p.Pro103Ala (c.307C>G) is classified Uncertain significance in SLC2A9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.0575); Rare (popmax 0.174%, eas); Associated with Inborn genetic diseases.

What condition is associated with SLC2A9 p.Pro103Ala (c.307C>G)?

SLC2A9 p.Pro103Ala (c.307C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SLC2A9 p.Pro103Ala (c.307C>G) in the general population?

SLC2A9 p.Pro103Ala (c.307C>G) is rare (popmax 0.174%, eas) (gnomAD).

What do computational predictors say about SLC2A9 p.Pro103Ala (c.307C>G)?

AlphaMissense predicts likely benign (score 0.0575) — an in-silico prediction, not a clinical call.

SLC2A9 p.Pro103Ala

c.307C>G · VCV3956418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0575 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.174%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0575	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.013	GERP -3
Regional constraint	o/e 1.01	unconstrained · MANE · 195 kb · p 0.75 · regional, not allelic
Overall
CADD	5.909	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.174% East Asian · 78/44,874 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.00483% 78/1,614,120 alleles · rare exomes 72/1,461,834 · genomes 6/152,286 · 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: SLC2A9
Protein: p.Pro103Ala
Coding: c.307C>G
MANE Select: NM_020041
Type: single nucleotide variant
Location: chr4:9996884 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.79 · 7 PDB
Residue 103: an α-helix

Full SLC2A9 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

Similar variants

SLC2A9 p.Arg447Trp Uncertain significance ★★ ⚠ same condition
SLC2A9 p.Asn144Ser Uncertain significance ★★ ⚠ same condition
SLC2A9 p.Ile149Val Uncertain significance ★★ ⚠ same condition
SLC2A9 p.Ile335Asn Uncertain significance ★★ ⚠ same condition
SLC2A9 p.Ile335Thr Uncertain significance ★★ ⚠ same condition
SLC2A9 p.Val180= Likely benign ★★ same condition
SLC2A9 p.Ala242Thr Uncertain significance ★ ⚠ same condition
SLC2A9 p.Ala464Ser 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/slc2a9-p-pro103ala (accessed [today's date]).

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