Is PRDM16 p.Ser148= (c.444C>T) pathogenic?

PRDM16 p.Ser148= (c.444C>T) is classified Benign in PRDM16 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele; Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ser148= (c.444C>T)?

PRDM16 p.Ser148= (c.444C>T) is associated with left ventricular noncompaction 8 (ClinVar).

How is Left ventricular noncompaction inherited?

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

PRDM16 p.Ser148=

Q: How common is PRDM16 p.Ser148= (c.444C>T) in the general population?

PRDM16 p.Ser148= (c.444C>T) is common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.444C>T · rs2282198 · VCV227041

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 59%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

left ventricular noncompaction 8

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 -10	GERP -5.5
Overall
CADD	0.903	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59% East Asian · 26,439/44,840 alleles

Filtering AF 58.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.1%

Overall 29% 468,012/1,613,150 alleles · common exomes 430,644/1,461,044 · genomes 37,368/152,106 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	59%	2
South Asian	52%	2
Admixed American	37.6%	3
Amishnot grpmax-eligible	31.1%	3
Middle Eastern	30.9%	3
Finnishnot grpmax-eligible	30.3%	3
Remaining individualsnot grpmax-eligible	29.8%	3
European (non-Finnish)	27.1%	4
Ashkenazi Jewishnot grpmax-eligible	21.7%	5
African / African-American	7.63%	13

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.Ser148=
Coding: c.444C>T
MANE Select: NM_022114
dbSNP: rs2282198
Type: single nucleotide variant
Location: chr1:3385157 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 148: the set domain

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 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-ser148 (accessed [today's date]).

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