Is SLC18A3 p.Val484Ala (c.1451T>C) pathogenic?

SLC18A3 p.Val484Ala (c.1451T>C) is classified Uncertain significance in SLC18A3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-16). AlphaMissense: likely benign (0.1955); Ultra-rare (popmax 0.0306%, afr); Associated with Inborn genetic diseases.

What condition is associated with SLC18A3 p.Val484Ala (c.1451T>C)?

SLC18A3 p.Val484Ala (c.1451T>C) is associated with Inborn genetic diseases (ClinVar).

How common is SLC18A3 p.Val484Ala (c.1451T>C) in the general population?

SLC18A3 p.Val484Ala (c.1451T>C) is ultra-rare (popmax 0.0306%, afr) (gnomAD).

What do computational predictors say about SLC18A3 p.Val484Ala (c.1451T>C)?

AlphaMissense predicts likely benign (score 0.1955) — an in-silico prediction, not a clinical call.

SLC18A3 p.Val484Ala

c.1451T>C · rs142761243 · VCV1435212

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0306%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1955	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 304 bp · p 0.11 · regional, not allelic
Overall
CADD	23.6	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 0.0306% African / African-American · 23/75,076 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0177%

Overall 0.00205% 33/1,609,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0306%	3,264
Admixed American	0.00666%	15,007
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.000169%	590,002

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.Val484Ala
Coding: c.1451T>C
MANE Select: NM_020549 · reported on NM_003055
dbSNP: rs142761243
Type: single nucleotide variant
Location: chr10:49612191 (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-val484ala (accessed [today's date]).

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