Is SLC18A3 p.Pro511Ser (c.1531C>T) pathogenic?

SLC18A3 p.Pro511Ser (c.1531C>T) is classified Uncertain significance in SLC18A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-26). AlphaMissense: likely benign (0.0749); Ultra-rare (popmax 0.0347%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC18A3 p.Pro511Ser (c.1531C>T)?

SLC18A3 p.Pro511Ser (c.1531C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SLC18A3 p.Pro511Ser (c.1531C>T) in the general population?

SLC18A3 p.Pro511Ser (c.1531C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

What do computational predictors say about SLC18A3 p.Pro511Ser (c.1531C>T)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

SLC18A3 p.Pro511Ser

c.1531C>T · rs139485937 · VCV1480361

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP 0.8, phastCons 0.012
Regional constraint	o/e 1.14	unconstrained · MANE · 304 bp · p 0.11 · regional, not allelic
Overall
CADD	14.3	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 0.0347% African / African-American · 26/74,916 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00217% 35/1,610,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,881
Middle Eastern	0.0164%	6,084
Admixed American	0.0117%	8,569
South Asian	0.0011%	91,024

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.Pro511Ser
Coding: c.1531C>T
MANE Select: NM_020549 · reported on NM_003055
dbSNP: rs139485937
Type: single nucleotide variant
Location: chr10:49612271 (GRCh38)

Full SLC18A3 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

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-pro511ser (accessed [today's date]).

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