Is PRDM5 p.Ser14= (c.42C>G) pathogenic?

PRDM5 p.Ser14= (c.42C>G) is classified Likely benign in PRDM5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-20). Ultra-rare (popmax 0.0829%, afr); Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Ser14= (c.42C>G)?

PRDM5 p.Ser14= (c.42C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Ser14= (c.42C>G) in the general population?

PRDM5 p.Ser14= (c.42C>G) is ultra-rare (popmax 0.0829%, afr) (gnomAD).

PRDM5 p.Ser14=

c.42C>G · rs141699988 · VCV1739520

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0829%, 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 0.057	GERP -2.6, phastCons 0.65
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0829% African / African-American · 62/74,820 alleles

Filtering AF 0.0663% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0603%

Overall 0.00422% 68/1,610,978 alleles · ultra-rare exomes 34/1,459,002 · genomes 34/151,976 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0829%	1,207
Remaining individualsnot grpmax-eligible	0.00642%	15,588
Admixed American	0.00167%	59,868
European (non-Finnish)	8.48e-05%	1,179,206

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.Ser14=
Coding: c.42C>G
MANE Select: NM_018699
dbSNP: rs141699988
Type: single nucleotide variant
Location: chr4:120922567 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB
Residue 14: 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.Ser14Ala 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-ser14 (accessed [today's date]).

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