Is PRDM16 p.Ala34= (c.102G>A) pathogenic?

PRDM16 p.Ala34= (c.102G>A) is classified Benign/Likely benign in PRDM16 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.135%, afr); Associated with left ventricular noncompaction 8.

What condition is associated with PRDM16 p.Ala34= (c.102G>A)?

PRDM16 p.Ala34= (c.102G>A) is associated with left ventricular noncompaction 8 (ClinVar).

How common is PRDM16 p.Ala34= (c.102G>A) in the general population?

PRDM16 p.Ala34= (c.102G>A) is rare (popmax 0.135%, afr) (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.Ala34=

c.102G>A · rs374918897 · VCV474401

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.135%, afr)

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 -9.4	GERP -3.3
Overall
CADD	0.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% African / African-American · 101/75,042 alleles

Filtering AF 0.113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0109% 176/1,612,880 alleles · rare exomes 121/1,460,550 · genomes 55/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.135%	743
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0096%	10,414
Admixed American	0.00833%	12,006
South Asian	0.00549%	18,216
European (non-Finnish)	0.00475%	21,071
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598

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.Ala34=
Coding: c.102G>A
MANE Select: NM_022114
dbSNP: rs374918897
Type: single nucleotide variant
Location: chr1:3186189 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 34: 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.Ala34Val Uncertain significance ★★ ⚠ same residue
PRDM16 p.Ala34Thr 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

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-ala34 (accessed [today's date]).

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