Is PRDM5 p.Gly485Arg (c.1453G>A) pathogenic?

PRDM5 p.Gly485Arg (c.1453G>A) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-16). AlphaMissense: likely pathogenic (0.9649); Very rare (popmax 8.48e-05%, nfe).

How common is PRDM5 p.Gly485Arg (c.1453G>A) in the general population?

PRDM5 p.Gly485Arg (c.1453G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PRDM5 p.Gly485Arg (c.1453G>A)?

AlphaMissense predicts likely pathogenic (score 0.9649) — an in-silico prediction, not a clinical call.

PRDM5 p.Gly485Arg

c.1453G>A · VCV4848496

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9649	likely pathogenic
REVEL	0.39	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	29.4	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,446 alleles

Overall 6.2e-05% 1/1,613,282 alleles · very rare exomes 1/1,461,094 · genomes 0/152,188 · joint denominator

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.Gly485Arg
Coding: c.1453G>A
MANE Select: NM_018699
Type: single nucleotide variant
Location: chr4:120777272 (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

Similar variants

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
PRDM5 p.Glu344Ter 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-gly485arg (accessed [today's date]).

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