Is SLC10A2 p.Ser15Pro (c.43T>C) pathogenic?

SLC10A2 p.Ser15Pro (c.43T>C) is classified Uncertain significance in SLC10A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-18). AlphaMissense: likely benign (0.1431); Ultra-rare (popmax 0.0446%, eas).

How common is SLC10A2 p.Ser15Pro (c.43T>C) in the general population?

SLC10A2 p.Ser15Pro (c.43T>C) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about SLC10A2 p.Ser15Pro (c.43T>C)?

AlphaMissense predicts likely benign (score 0.1431) — an in-silico prediction, not a clinical call.

SLC10A2 p.Ser15Pro

c.43T>C · rs551355092 · VCV2471538

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1431 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1431	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.95	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 -4.2	GERP -3.5
Regional constraint	o/e 1.19	unconstrained · MANE · 20 kb · p 4.9e-05 · regional, not allelic
Overall
CADD	0.203	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 0.0446% East Asian · 20/44,868 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00124% 20/1,613,868 alleles · ultra-rare exomes 16/1,461,528 · genomes 4/152,340 · 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: SLC10A2
Protein: p.Ser15Pro
Coding: c.43T>C
MANE Select: NM_000452
dbSNP: rs551355092
Type: single nucleotide variant
Location: chr13:103066207 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.88

Full SLC10A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC10A2 p.Ser15= Conflicting classifications of pathogenicity ★ same residue
SLC10A2 p.Ala111Val Uncertain significance ★★ ⚠ same type
SLC10A2 p.Ala116Val Uncertain significance ★★ ⚠ same type
SLC10A2 p.Ala202Ser Uncertain significance ★★ ⚠ same type
SLC10A2 p.Ala202Thr Uncertain significance ★★ ⚠ same type
SLC10A2 p.Ala302Thr Uncertain significance ★★ ⚠ same type
SLC10A2 p.Ala43Val Uncertain significance ★★ same type
SLC10A2 p.Arg246Thr 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/slc10a2-p-ser15pro (accessed [today's date]).

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