Is PRDM5 p.Asp321= (c.963T>C) pathogenic?

PRDM5 p.Asp321= (c.963T>C) is classified Benign/Likely benign in PRDM5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.91%, afr); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Asp321= (c.963T>C)?

PRDM5 p.Asp321= (c.963T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Asp321= (c.963T>C) in the general population?

PRDM5 p.Asp321= (c.963T>C) is low-frequency (popmax 2.91%, afr) (gnomAD).

PRDM5 p.Asp321=

c.963T>C · rs34666716 · VCV390576

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.91%, afr)

Conditions

Cardiovascular phenotype

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 1.3	GERP -1.1, phastCons 1
Overall
CADD	8.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.91% African / African-American · 2,180/74,992 alleles

Filtering AF 2.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.76%

Overall 0.156% 2,512/1,612,718 alleles · low-frequency exomes 1,199/1,460,434 · genomes 1,313/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.91%	34
Admixed American	0.269%	372
Remaining individualsnot grpmax-eligible	0.2%	499
Middle Eastern	0.0524%	1,908
South Asian	0.0341%	2,934
European (non-Finnish)	0.00102%	98,291

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: PRDM5
Protein: p.Asp321=
Coding: c.963T>C
MANE Select: NM_018699
dbSNP: rs34666716
Type: single nucleotide variant
Location: chr4:120799728 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB

Full PRDM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDM5 p.Gln556Ter Pathogenic/Likely pathogenic ★★ same condition
PRDM5 c.650+5G>A Uncertain significance ★★ same condition
PRDM5 c.744-3T>C Uncertain significance ★★ same condition
PRDM5 p.Ala155Val Uncertain significance ★★ ⚠ same condition
PRDM5 p.Ala469Val Uncertain significance ★★ same condition
PRDM5 p.Arg257Pro Uncertain significance ★★ ⚠ same condition
PRDM5 p.Arg257Trp Uncertain significance ★★ ⚠ same condition
PRDM5 p.Arg261Ser 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/prdm5-p-asp321 (accessed [today's date]).

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