Is PRDM16 p.Ser596Arg (c.1788C>G) pathogenic?

PRDM16 p.Ser596Arg (c.1788C>G) is classified Uncertain significance in PRDM16 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: ambiguous (0.5455); Absent from gnomAD v4.1; Associated with dilated cardiomyopathy.

What condition is associated with PRDM16 p.Ser596Arg (c.1788C>G)?

PRDM16 p.Ser596Arg (c.1788C>G) is associated with dilated cardiomyopathy (ClinVar).

How common is PRDM16 p.Ser596Arg (c.1788C>G) in the general population?

PRDM16 p.Ser596Arg (c.1788C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM16 p.Ser596Arg (c.1788C>G)?

AlphaMissense predicts ambiguous (score 0.5455) — an in-silico prediction, not a clinical call.

PRDM16 p.Ser596Arg

c.1788C>G · rs766972389 · VCV1526272

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.5455	ambiguous
REVEL	0.087	moderately benign-leaning
SaProt	LLR -7.37	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -4.9
Regional constraint	o/e 1.03	unconstrained · MANE · 6,505 bp · p 0.39 · regional, not allelic
Overall
CADD	11.28	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.Ser596Arg
Coding: c.1788C>G
MANE Select: NM_022114
dbSNP: rs766972389
Type: single nucleotide variant
Location: chr1:3411985 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 596: the 'disordered' region

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

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDM16 p.Ser596= Likely benign ★★ same residue
PRDM16 p.Ser596Asn Uncertain significance ★ ⚠ same residue
PRDM16 p.Arg26Trp Uncertain significance ★★ ⚠ same condition
PRDM16 p.Met788Leu Uncertain significance ★★ ⚠ same condition
PRDM16 p.Pro291Leu Uncertain significance ★★ ⚠ same condition
PRDM16 p.Ala1052Thr Likely benign ★★ same condition
PRDM16 c.388-2A>G Uncertain significance ★★ same type
PRDM16 p.Ala1035Ser Uncertain significance ★★ ⚠ same type

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-ser596arg (accessed [today's date]).

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