Is PRDM5 p.Pro403= (c.1209G>A) pathogenic?

PRDM5 p.Pro403= (c.1209G>A) is classified Likely benign in PRDM5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-04). Ultra-rare (popmax 0.0134%, eas); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Pro403= (c.1209G>A)?

PRDM5 p.Pro403= (c.1209G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Pro403= (c.1209G>A) in the general population?

PRDM5 p.Pro403= (c.1209G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

PRDM5 p.Pro403=

c.1209G>A · rs748165562 · VCV1749570

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

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 -13	GERP -4.6
Overall
CADD	4.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,844 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00118% 19/1,611,148 alleles · ultra-rare exomes 18/1,459,132 · genomes 1/152,016 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,474
Admixed American	0.00334%	29,931
South Asian	0.0022%	45,520
European (non-Finnish)	0.000764%	130,864

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.Pro403=
Coding: c.1209G>A
MANE Select: NM_018699
dbSNP: rs748165562
Type: single nucleotide variant
Location: chr4:120785071 (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.Pro403Leu Uncertain significance ★★ ⚠ same residue
PRDM5 p.Pro403Arg 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

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-pro403 (accessed [today's date]).

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