Is PRDM16 p.Val751= (c.2253C>G) pathogenic?

PRDM16 p.Val751= (c.2253C>G) is classified Likely benign in PRDM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Very rare (popmax 0.00133%, afr); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Val751= (c.2253C>G)?

PRDM16 p.Val751= (c.2253C>G) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Val751= (c.2253C>G) in the general population?

PRDM16 p.Val751= (c.2253C>G) is very rare (popmax 0.00133%, 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.Val751=

c.2253C>G · rs1159303119 · VCV2718294

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 2.2	GERP -3.4, phastCons 1
Overall
CADD	7.815	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Overall 0.000124% 2/1,613,196 alleles · very rare exomes 1/1,460,996 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-Americangrpmax	0.00133%	74,922

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val751=
Coding: c.2253C>G
MANE Select: NM_022114
dbSNP: rs1159303119
Type: single nucleotide variant
Location: chr1:3412450 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 751: 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-val751 (accessed [today's date]).

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