Is PRDM5 p.Asp445Val (c.1334A>T) pathogenic?

PRDM5 p.Asp445Val (c.1334A>T) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-02). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with PRDM5 p.Asp445Val (c.1334A>T)?

PRDM5 p.Asp445Val (c.1334A>T) is associated with Cardiovascular phenotype (ClinVar).

How common is PRDM5 p.Asp445Val (c.1334A>T) in the general population?

PRDM5 p.Asp445Val (c.1334A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM5 p.Asp445Val (c.1334A>T)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

PRDM5 p.Asp445Val

c.1334A>T · rs2477152427 · VCV3227138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic · top 8% in PRDM5
REVEL	0.509	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM5
Protein: p.Asp445Val
Coding: c.1334A>T
MANE Select: NM_018699
dbSNP: rs2477152427
Type: single nucleotide variant
Location: chr4:120781252 (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-asp445val (accessed [today's date]).

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