Is PRDM16 p.Ser13= (c.39T>C) pathogenic?

PRDM16 p.Ser13= (c.39T>C) is classified Conflicting classifications of pathogenicity in PRDM16 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-10-05). Very rare (popmax 0.00223%, eas); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ser13= (c.39T>C)?

PRDM16 p.Ser13= (c.39T>C) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser13= (c.39T>C) in the general population?

PRDM16 p.Ser13= (c.39T>C) is very rare (popmax 0.00223%, eas) (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.Ser13=

c.39T>C · rs1373869540 · VCV700796

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

left ventricular noncompaction 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.9	phastCons 1
Overall
CADD	15.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,856 alleles

Overall 0.000124% 2/1,611,696 alleles · very rare exomes 2/1,459,456 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,856
Remaining individualsnot grpmax-eligible	0.0016%	62,448

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.Ser13=
Coding: c.39T>C
MANE Select: NM_022114
dbSNP: rs1373869540
Type: single nucleotide variant
Location: chr1:3186126 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 13: the 'disordered' region

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 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
PRDM16 p.Ala175Val Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala34Val 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-ser13 (accessed [today's date]).

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