Is PRDM16 p.Ser797Pro (c.2389T>C) pathogenic?

PRDM16 p.Ser797Pro (c.2389T>C) is classified Uncertain significance in PRDM16 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-04). AlphaMissense: likely benign (0.0693); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRDM16 p.Ser797Pro (c.2389T>C)?

PRDM16 p.Ser797Pro (c.2389T>C) is associated with Inborn genetic diseases, left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser797Pro (c.2389T>C) in the general population?

PRDM16 p.Ser797Pro (c.2389T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM16 p.Ser797Pro (c.2389T>C)?

AlphaMissense predicts likely benign (score 0.0693) — an in-silico prediction, not a clinical call.

PRDM16 p.Ser797Pro

c.2389T>C · rs2100664655 · VCV1438286

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0693 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0693	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.89	GERP -4.2
Regional constraint	o/e 1.03	unconstrained · MANE · 6,505 bp · p 0.39 · regional, not allelic
Overall
CADD	7.762	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ser797Pro
Coding: c.2389T>C
MANE Select: NM_022114
dbSNP: rs2100664655
Type: single nucleotide variant
Location: chr1:3412586 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 797: the 'interaction with ctbp1, ctbp2 and znf516' region; the 'mediates interaction with ski and regulation of tgf-beta signaling' region; the 'disordered' region; a UniProt-annotated variant site (in lvnc8)

Full PRDM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: left ventricular noncompaction 8

Similar variants

PRDM16 p.Ser797= Benign/Likely benign ★★ 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-ser797pro (accessed [today's date]).

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