Is PRDM16 p.Ser940= (c.2820C>T) pathogenic?

PRDM16 p.Ser940= (c.2820C>T) is classified Likely benign in PRDM16 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.0165%, mid); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ser940= (c.2820C>T)?

PRDM16 p.Ser940= (c.2820C>T) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser940= (c.2820C>T) in the general population?

PRDM16 p.Ser940= (c.2820C>T) is ultra-rare (popmax 0.0165%, mid) (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.Ser940=

c.2820C>T · rs764764989 · VCV509306

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 -7.4	GERP -4.5
Overall
CADD	0.275	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00149% 24/1,613,004 alleles · ultra-rare exomes 23/1,460,784 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
East Asian	0.0134%	7,477
South Asian	0.00659%	15,175
Admixed American	0.00167%	59,978
Finnishnot grpmax-eligible	0.00158%	63,348
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000678%	147,479

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.Ser940=
Coding: c.2820C>T
MANE Select: NM_022114
dbSNP: rs764764989
Type: single nucleotide variant
Location: chr1:3417956 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 940: the 'interaction with ctbp1, ctbp2 and znf516' region; the 'mediates interaction with ski and regulation of tgf-beta signaling' region; a UniProt-annotated variant site (in lvnc8)

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-ser940 (accessed [today's date]).

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