Is PRDM16 p.Lys915Glu (c.2743A>G) pathogenic?

PRDM16 p.Lys915Glu (c.2743A>G) is classified Uncertain significance in PRDM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-03). AlphaMissense: ambiguous (0.557); Absent from gnomAD v4.1; Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Lys915Glu (c.2743A>G)?

PRDM16 p.Lys915Glu (c.2743A>G) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Lys915Glu (c.2743A>G) in the general population?

PRDM16 p.Lys915Glu (c.2743A>G) is absent from gnomAD v4.1 (gnomAD).

How is Left ventricular noncompaction inherited?

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

What do computational predictors say about PRDM16 p.Lys915Glu (c.2743A>G)?

AlphaMissense predicts ambiguous (score 0.557) — an in-silico prediction, not a clinical call.

PRDM16 p.Lys915Glu

c.2743A>G · rs1638313904 · VCV2132586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.557 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

left ventricular noncompaction 8

Computational evidence

Protein change
AlphaMissense	0.557	ambiguous
REVEL	0.382	indeterminate
SaProt	LLR -9.59	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 6,505 bp · p 0.39 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM16
Protein: p.Lys915Glu
Coding: c.2743A>G
MANE Select: NM_022114
dbSNP: rs1638313904
Type: single nucleotide variant
Location: chr1:3417879 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 915: the 'interaction with ctbp1, ctbp2 and znf516' region; the 'mediates interaction with ski and regulation of tgf-beta signaling' region; a modified residue (n6-acetyllysine; alternate); a cross-link site; 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 p.Lys915Gln 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
PRDM16 p.Ala175Val 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-lys915glu (accessed [today's date]).

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