Is SLC18A3 p.Pro281= (c.843C>G) pathogenic?

SLC18A3 p.Pro281= (c.843C>G) is classified Likely benign in SLC18A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Very rare (popmax 0.00602%, nfe).

How common is SLC18A3 p.Pro281= (c.843C>G) in the general population?

SLC18A3 p.Pro281= (c.843C>G) is very rare (popmax 0.00602%, nfe) (gnomAD).

SLC18A3 p.Pro281=

c.843C>G · rs775965436 · VCV2960029

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.091	GERP -3.7, phastCons 0.93
Overall
CADD	9.059	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00602% European (non-Finnish) · 71/1,179,992 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00472% 76/1,608,992 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Finnishnot grpmax-eligible	0.00508%	19,677
Remaining individualsnot grpmax-eligible	0.0032%	31,217

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: SLC18A3
Protein: p.Pro281=
Coding: c.843C>G
MANE Select: NM_020549 · reported on NM_003055
dbSNP: rs775965436
Type: single nucleotide variant
Location: chr10:49611583 (GRCh38)

Full SLC18A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/slc18a3-p-pro281 (accessed [today's date]).

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