Is PRDM5 p.Ala98= (c.294C>A) pathogenic?

PRDM5 p.Ala98= (c.294C>A) is classified Likely benign in PRDM5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-28). Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Ala98= (c.294C>A)?

PRDM5 p.Ala98= (c.294C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Ala98= (c.294C>A) in the general population?

PRDM5 p.Ala98= (c.294C>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PRDM5 p.Ala98=

c.294C>A · rs1578994254 · VCV744515

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 3.2	phastCons 1
Overall
CADD	9.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,700 alleles

Overall 6.2e-05% 1/1,613,722 alleles · very rare exomes 1/1,461,434 · genomes 0/152,288 · joint denominator

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.Ala98=
Coding: c.294C>A
MANE Select: NM_018699
dbSNP: rs1578994254
Type: single nucleotide variant
Location: chr4:120853424 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB
Residue 98: the set domain; a β-strand

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.Ala98Thr Uncertain significance ★ same residue
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

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-ala98 (accessed [today's date]).

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