Is PRDM5 p.Arg83Ser (c.247C>A) pathogenic?

PRDM5 p.Arg83Ser (c.247C>A) is classified Uncertain significance in PRDM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). AlphaMissense: likely pathogenic (0.8951); Very rare (popmax 0.00017%, nfe).

How common is PRDM5 p.Arg83Ser (c.247C>A) in the general population?

PRDM5 p.Arg83Ser (c.247C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PRDM5 p.Arg83Ser (c.247C>A)?

AlphaMissense predicts likely pathogenic (score 0.8951) — an in-silico prediction, not a clinical call.

PRDM5 p.Arg83Ser

c.247C>A · VCV4540996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8951 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8951	likely pathogenic
REVEL	0.423	indeterminate
SaProt	LLR -8.07	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 145 kb · p 0.23 · regional, not allelic
Overall
CADD	29.7	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 0.00017% European (non-Finnish) · 2/1,179,760 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,642 alleles · very rare exomes 1/1,461,494 · genomes 1/152,148 · 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.Arg83Ser
Coding: c.247C>A
MANE Select: NM_018699
Type: single nucleotide variant
Location: chr4:120853471 (GRCh38)
Gene constraint: LOEUF 0.899 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.53 · 1 PDB
Residue 83: the set domain; an α-helix

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

Similar variants

PRDM5 p.Arg83Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
PRDM5 p.Arg83His Conflicting classifications of pathogenicity ★ same residue
PRDM5 p.Arg83= Likely benign ★ same residue
PRDM5 p.Arg83fs Pathogenic ★ 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

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-arg83ser (accessed [today's date]).

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