Is PRDM16 p.Ser533= (c.1599G>A) pathogenic?

PRDM16 p.Ser533= (c.1599G>A) is classified Benign/Likely benign in PRDM16 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Rare (popmax 0.194%, afr); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ser533= (c.1599G>A)?

PRDM16 p.Ser533= (c.1599G>A) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser533= (c.1599G>A) in the general population?

PRDM16 p.Ser533= (c.1599G>A) is rare (popmax 0.194%, afr) (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRDM16 p.Ser533=

c.1599G>A · rs373205864 · VCV413858

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.194%, afr)

Conditions

left ventricular noncompaction 8

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 -4.1	GERP -4.5
Overall
CADD	0.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.194% African / African-American · 145/74,928 alleles

Filtering AF 0.168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.0135% 217/1,611,442 alleles · rare exomes 135/1,459,424 · genomes 82/152,018 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.194%	517
Middle Eastern	0.033%	3,026
Remaining individualsnot grpmax-eligible	0.0304%	3,288
Admixed American	0.005%	19,995
East Asian	0.00446%	22,415
South Asian	0.00439%	22,760
European (non-Finnish)	0.00348%	28,772
Finnishnot grpmax-eligible	0.00161%	61,986

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: PRDM16
Protein: p.Ser533=
Coding: c.1599G>A
MANE Select: NM_022114
dbSNP: rs373205864
Type: single nucleotide variant
Location: chr1:3411796 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 533: the 'disordered' region; a UniProt-annotated variant site (in)

Full PRDM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

left ventricular noncompaction 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

PRDM16 p.Ser533Pro Benign ★★ same residue
PRDM16 p.Ser533Leu Uncertain significance ★ same residue
PRDM16 c.388-2A>G Uncertain significance ★★ same condition
PRDM16 p.Ala1035Ser Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala1096Thr Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala1096Val Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala1146Thr 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/prdm16-p-ser533 (accessed [today's date]).

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