Is PRDM16 p.Ser623= (c.1869G>A) pathogenic?

PRDM16 p.Ser623= (c.1869G>A) is classified Likely benign in PRDM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-29). Very rare (popmax 0.00663%, sas); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ser623= (c.1869G>A)?

PRDM16 p.Ser623= (c.1869G>A) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser623= (c.1869G>A) in the general population?

PRDM16 p.Ser623= (c.1869G>A) is very rare (popmax 0.00663%, sas) (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.Ser623=

c.1869G>A · rs778188314 · VCV1611252

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00663%, sas)

Conditions

left ventricular noncompaction 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -16	GERP -4.9
Overall
CADD	0.598	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00663% South Asian · 6/90,484 alleles

Filtering AF 0.00288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.0028% 45/1,604,816 alleles · very rare exomes 40/1,452,644 · genomes 5/152,172 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00663%	15,081
Ashkenazi Jewishnot grpmax-eligible	0.00343%	29,178
European (non-Finnish)	0.00298%	33,547
African / African-American	0.00268%	37,346
Admixed American	0.00168%	59,508

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.Ser623=
Coding: c.1869G>A
MANE Select: NM_022114
dbSNP: rs778188314
Type: single nucleotide variant
Location: chr1:3412066 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 623: the 'disordered' region

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.Ser623Leu 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-ser623 (accessed [today's date]).

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