Is PRDM16 p.Ser718= (c.2154G>A) pathogenic?

PRDM16 p.Ser718= (c.2154G>A) is classified Likely benign in PRDM16 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-12). Ultra-rare (popmax 0.0493%, mid); Associated with Inborn genetic diseases.

What condition is associated with PRDM16 p.Ser718= (c.2154G>A)?

PRDM16 p.Ser718= (c.2154G>A) is associated with Inborn genetic diseases, left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ser718= (c.2154G>A) in the general population?

PRDM16 p.Ser718= (c.2154G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

PRDM16 p.Ser718=

c.2154G>A · rs781041726 · VCV517157

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

Inborn genetic diseases

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 -13	GERP -4.6
Overall
CADD	0.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00421% 68/1,613,454 alleles · ultra-rare exomes 48/1,461,266 · genomes 20/152,188 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
African / African-American	0.0294%	3,406
Remaining individualsnot grpmax-eligible	0.0208%	4,806
Admixed American	0.01%	10,001
South Asian	0.00329%	30,363
European (non-Finnish)	0.00178%	56,192

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.Ser718=
Coding: c.2154G>A
MANE Select: NM_022114
dbSNP: rs781041726
Type: single nucleotide variant
Location: chr1:3412351 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 718: the 'interaction with ctbp1, ctbp2 and znf516' 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 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
PRDM16 p.Ala34Val 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-ser718 (accessed [today's date]).

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