Is SLC45A1 p.Pro445= (c.1335G>A) pathogenic?

SLC45A1 p.Pro445= (c.1335G>A) is classified Benign in SLC45A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). Common (popmax 52%, afr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual developmental disorder with neuropsychiatric features.

What condition is associated with SLC45A1 p.Pro445= (c.1335G>A)?

SLC45A1 p.Pro445= (c.1335G>A) is associated with intellectual developmental disorder with neuropsychiatric features (ClinVar).

SLC45A1 p.Pro445=

Q: How common is SLC45A1 p.Pro445= (c.1335G>A) in the general population?

SLC45A1 p.Pro445= (c.1335G>A) is common (popmax 52%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1335G>A · rs2289731 · VCV2585663

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 52%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual developmental disorder with neuropsychiatric features

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -3.4
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52% African / African-American · 38,955/74,960 alleles

Filtering AF 51.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 51.4%

Overall 31.5% 508,270/1,613,096 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	52%	2
Middle Eastern	44.1%	2
Ashkenazi Jewishnot grpmax-eligible	41.4%	2
Amishnot grpmax-eligible	35.6%	3
Remaining individualsnot grpmax-eligible	33.2%	3
European (non-Finnish)	31.2%	3
South Asian	30.7%	3
Admixed American	27.4%	4
Finnishnot grpmax-eligible	20.7%	5
East Asian	17%	6

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: SLC45A1
Protein: p.Pro445=
Coding: c.1335G>A
MANE Select: NM_001080397
dbSNP: rs2289731
Type: single nucleotide variant
Location: chr1:8330828 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.26

Full SLC45A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with neuropsychiatric features — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SLC45A1 p.Arg42Trp Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Arg670Gln Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Gly393Asp Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Phe272Leu Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Pro312Leu Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Thr29Met Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Val490Met Uncertain significance ★★ ⚠ same condition
SLC45A1 p.Val528Ile Uncertain significance ★★ ⚠ 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/slc45a1-p-pro445 (accessed [today's date]).

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