Is SLC28A3 p.Ser32Pro (c.94T>C) pathogenic?

SLC28A3 p.Ser32Pro (c.94T>C) is classified Uncertain significance in SLC28A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.0688); Ultra-rare (popmax 0.075%, amr).

How common is SLC28A3 p.Ser32Pro (c.94T>C) in the general population?

SLC28A3 p.Ser32Pro (c.94T>C) is ultra-rare (popmax 0.075%, amr) (gnomAD).

What do computational predictors say about SLC28A3 p.Ser32Pro (c.94T>C)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

SLC28A3 p.Ser32Pro

c.94T>C · rs1051545233 · VCV2392943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.075%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.79	GERP -1.2, phastCons 0.012
Regional constraint	o/e 0.85	unconstrained · MANE · 62 kb · p 8.1e-06 · regional, not allelic
Overall
CADD	7.105	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 0.075% Admixed American · 45/59,978 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00279% 45/1,613,890 alleles · ultra-rare exomes 17/1,461,808 · genomes 28/152,082 · 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: SLC28A3
Protein: p.Ser32Pro
Coding: c.94T>C
MANE Select: NM_001199633
dbSNP: rs1051545233
Type: single nucleotide variant
Location: chr9:84313421 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.28 · 1 PDB
Residue 32: the 'disordered' region

Full SLC28A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC28A3 p.Ala392= Benign ★★ same type
SLC28A3 p.Leu461= Benign ★★ same type
SLC28A3 p.Ser374= Benign ★★ same type
SLC28A3 p.Ser5Asn Benign ★★ same type
SLC28A3 p.Ala190Pro Uncertain significance ★ ⚠ same type
SLC28A3 p.Ala362Thr Uncertain significance ★ ⚠ same type
SLC28A3 p.Ala366Thr Uncertain significance ★ ⚠ same type
SLC28A3 p.Ala451Thr Uncertain significance ★ ⚠ 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/slc28a3-p-ser32pro (accessed [today's date]).

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