Is PRDM13 p.Pro396Arg (c.1187C>G) pathogenic?

PRDM13 p.Pro396Arg (c.1187C>G) is classified Uncertain significance in PRDM13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-12). AlphaMissense: likely benign (0.0929); Ultra-rare (popmax 0.0374%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRDM13 p.Pro396Arg (c.1187C>G)?

PRDM13 p.Pro396Arg (c.1187C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRDM13 p.Pro396Arg (c.1187C>G) in the general population?

PRDM13 p.Pro396Arg (c.1187C>G) is ultra-rare (popmax 0.0374%, eas) (gnomAD).

What do computational predictors say about PRDM13 p.Pro396Arg (c.1187C>G)?

AlphaMissense predicts likely benign (score 0.0929) — an in-silico prediction, not a clinical call.

PRDM13 p.Pro396Arg

c.1187C>G · rs527649781 · VCV1501135

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0929 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0374%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0929	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP 0.52
Regional constraint	o/e 1.06	unconstrained · MANE · 7,424 bp · p 0.058 · regional, not allelic
Overall
CADD	15.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0374% East Asian · 14/37,482 alleles

Filtering AF 0.0226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00503% 76/1,511,136 alleles · ultra-rare exomes 74/1,359,004 · genomes 2/152,132 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0374%	2,677
European (non-Finnish)	0.00536%	18,640
Remaining individualsnot grpmax-eligible	0.0017%	58,710

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.Pro396Arg
Coding: c.1187C>G
MANE Select: NM_021620
dbSNP: rs527649781
Type: single nucleotide variant
Location: chr6:99613822 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDM13 p.Pro396Thr Uncertain significance ★★ ⚠ same residue
PRDM13 p.Pro396Ser Uncertain significance ★★ ⚠ same residue
PRDM13 p.Pro396Gln Uncertain significance ★ ⚠ same residue
PRDM13 p.Pro396= Likely benign ★ same residue
PRDM13 p.Pro396Ala Uncertain significance ⚠ same residue
PRDM13 p.Ala231Val Uncertain significance ★★ ⚠ same condition
PRDM13 p.Ala298Pro Uncertain significance ★★ ⚠ same condition
PRDM13 p.Ala510Thr 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/prdm13-p-pro396arg (accessed [today's date]).

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