Is PRDM5 p.Pro209= (c.627A>G) pathogenic?

PRDM5 p.Pro209= (c.627A>G) is classified Likely benign in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-04). Very rare (popmax 0.00934%, afr); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Pro209= (c.627A>G)?

PRDM5 p.Pro209= (c.627A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Pro209= (c.627A>G) in the general population?

PRDM5 p.Pro209= (c.627A>G) is very rare (popmax 0.00934%, afr) (gnomAD).

PRDM5 p.Pro209=

c.627A>G · rs138170787 · VCV1752571

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00934%, 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 -2.9	GERP -3.2
Overall
CADD	5.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,956 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000744% 12/1,613,948 alleles · very rare exomes 10/1,461,686 · genomes 2/152,262 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,708
Remaining individualsnot grpmax-eligible	0.0048%	20,825
South Asian	0.0022%	45,544

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.Pro209=
Coding: c.627A>G
MANE Select: NM_018699
dbSNP: rs138170787
Type: single nucleotide variant
Location: chr4:120818376 (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-pro209 (accessed [today's date]).

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