Is PRDM16 p.Arg357= (c.1071C>T) pathogenic?

PRDM16 p.Arg357= (c.1071C>T) is classified Benign in PRDM16 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.82%, afr); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Arg357= (c.1071C>T)?

PRDM16 p.Arg357= (c.1071C>T) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Arg357= (c.1071C>T) in the general population?

PRDM16 p.Arg357= (c.1071C>T) is low-frequency (popmax 2.82%, 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.Arg357=

c.1071C>T · rs2483221 · VCV221025

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.82%, 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 0.81	GERP -3.7, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.82% African / African-American · 2,104/74,490 alleles

Filtering AF 2.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.68%

Overall 0.173% 2,779/1,603,902 alleles · low-frequency exomes 1,468/1,451,600 · genomes 1,311/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.82%	35
Admixed American	0.3%	333
Middle Eastern	0.266%	376
Remaining individualsnot grpmax-eligible	0.256%	391
Ashkenazi Jewishnot grpmax-eligible	0.0652%	1,535
South Asian	0.0523%	1,913
European (non-Finnish)	0.0219%	4,575
Finnishnot grpmax-eligible	0.0016%	62,634

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.Arg357=
Coding: c.1071C>T
MANE Select: NM_022114
dbSNP: rs2483221
Type: single nucleotide variant
Location: chr1:3405533 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB

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.Arg357Cys Uncertain significance ★ ⚠ same residue
PRDM16 p.Arg357His 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-arg357 (accessed [today's date]).

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