Is PRDM13 p.Arg538Pro (c.1613G>C) pathogenic?

PRDM13 p.Arg538Pro (c.1613G>C) is classified Uncertain significance in PRDM13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-26). AlphaMissense: ambiguous (0.4314); Ultra-rare (popmax 0.0184%, amr).

How common is PRDM13 p.Arg538Pro (c.1613G>C) in the general population?

PRDM13 p.Arg538Pro (c.1613G>C) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

What do computational predictors say about PRDM13 p.Arg538Pro (c.1613G>C)?

AlphaMissense predicts ambiguous (score 0.4314) — an in-silico prediction, not a clinical call.

PRDM13 p.Arg538Pro

c.1613G>C · rs750792897 · VCV1919489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4314	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -5.54	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.1	GERP 0.75, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 7,424 bp · p 0.058 · regional, not allelic
Overall
CADD	27.4	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 0.0184% Admixed American · 11/59,806 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00798%

Overall 0.000746% 12/1,609,062 alleles · ultra-rare exomes 8/1,456,878 · genomes 4/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0184%	5,437
European (non-Finnish)	8.48e-05%	1,178,700

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: PRDM13
Protein: p.Arg538Pro
Coding: c.1613G>C
MANE Select: NM_021620
dbSNP: rs750792897
Type: single nucleotide variant
Location: chr6:99614248 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 53.52

Full PRDM13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM13 c.277-10T>G Uncertain significance ★★ same type
PRDM13 p.Ala231Val Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala258Val Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala298Pro Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala414Glu Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala510Thr Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala566Thr Uncertain significance ★★ ⚠ same type
PRDM13 p.Ala5Ser Uncertain significance ★★ ⚠ 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/prdm13-p-arg538pro (accessed [today's date]).

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