Is PRDM5 p.Val60Phe (c.178G>T) pathogenic?

PRDM5 p.Val60Phe (c.178G>T) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.8613); Absent from gnomAD v4.1.

How common is PRDM5 p.Val60Phe (c.178G>T) in the general population?

PRDM5 p.Val60Phe (c.178G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM5 p.Val60Phe (c.178G>T)?

AlphaMissense predicts likely pathogenic (score 0.8613) — an in-silico prediction, not a clinical call.

PRDM5 p.Val60Phe

c.178G>T · VCV3723469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8613 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8613	likely pathogenic
REVEL	0.622	indeterminate
SaProt	LLR -11.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Val60Phe
Coding: c.178G>T
MANE Select: NM_018699
Type: single nucleotide variant
Location: chr4:120853540 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB
Residue 60: the set domain; a β-strand

Full PRDM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM5 p.Val60= Likely benign ★ same residue
PRDM5 c.1623+1G>A Likely pathogenic ★★ same type
PRDM5 c.865+1G>A Likely pathogenic ★★ same type
PRDM5 p.Arg232Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Arg346Ter Pathogenic ★★ same type
PRDM5 p.Gln420Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Gln556Ter Pathogenic/Likely pathogenic ★★ same type
PRDM5 p.Glu103Ter Pathogenic/Likely pathogenic ★★ same type

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-val60phe (accessed [today's date]).

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