Is SLC45A2 p.Cys519Arg (c.1555T>C) pathogenic?

SLC45A2 p.Cys519Arg (c.1555T>C) is classified Likely pathogenic in SLC45A2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely pathogenic (0.9551); Very rare (popmax 0.00381%, nfe); Associated with SLC45A2-related disorder.

What condition is associated with SLC45A2 p.Cys519Arg (c.1555T>C)?

SLC45A2 p.Cys519Arg (c.1555T>C) is associated with SLC45A2-related disorder (ClinVar).

How common is SLC45A2 p.Cys519Arg (c.1555T>C) in the general population?

SLC45A2 p.Cys519Arg (c.1555T>C) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about SLC45A2 p.Cys519Arg (c.1555T>C)?

AlphaMissense predicts likely pathogenic (score 0.9551) — an in-silico prediction, not a clinical call.

SLC45A2 p.Cys519Arg

c.1555T>C · rs750510834 · VCV1939785

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9551 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SLC45A2-related disorder

Computational evidence

Protein change
AlphaMissense	0.9551	likely pathogenic ✓ concordant with ClinVar · top 6% in SLC45A2
REVEL	0.83	moderately pathogenic-leaning
SaProt	LLR -13.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.92, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 40 kb · p 0.064 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00381% European (non-Finnish) · 45/1,180,038 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00297% 48/1,614,102 alleles · very rare exomes 45/1,461,886 · genomes 3/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,223
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,936

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: SLC45A2
Protein: p.Cys519Arg
Coding: c.1555T>C
MANE Select: NM_016180
dbSNP: rs750510834
Type: single nucleotide variant
Location: chr5:33944686 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.96

Full SLC45A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SLC45A2-related disorder

Similar variants

SLC45A2 p.Cys519Phe Uncertain significance ★ ⚠ same residue
SLC45A2 p.Cys519Tyr Uncertain significance ★ ⚠ same residue
SLC45A2 c.1156+1G>C Pathogenic/Likely pathogenic ★★ same condition
SLC45A2 p.Ala511Glu Pathogenic ★★ same condition
SLC45A2 p.Asn122Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC45A2 p.Asp160His Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC45A2 p.Asp93Asn Pathogenic ★★ same condition
SLC45A2 p.Gly349Arg Pathogenic ★★ same condition

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/slc45a2-p-cys519arg (accessed [today's date]).

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