Is PRDM13 p.Pro89Ser (c.265C>T) pathogenic?

PRDM13 p.Pro89Ser (c.265C>T) is classified Uncertain significance in PRDM13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). AlphaMissense: likely pathogenic (0.6931); Very rare (popmax 6.2e-05%).

How common is PRDM13 p.Pro89Ser (c.265C>T) in the general population?

PRDM13 p.Pro89Ser (c.265C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about PRDM13 p.Pro89Ser (c.265C>T)?

AlphaMissense predicts likely pathogenic (score 0.6931) — an in-silico prediction, not a clinical call.

PRDM13 p.Pro89Ser

c.265C>T · rs368251086 · VCV1961532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6931	likely pathogenic
REVEL	0.372	indeterminate
SaProt	LLR -9.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 7,424 bp · p 0.058 · regional, not allelic
Overall
CADD	23.5	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 6.2e-05%

Overall 6.2e-05% 1/1,613,156 alleles · very rare exomes 1/1,460,948 · genomes 0/152,208 · 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: PRDM13
Protein: p.Pro89Ser
Coding: c.265C>T
MANE Select: NM_021620
dbSNP: rs368251086
Type: single nucleotide variant
Location: chr6:99608861 (GRCh38)
Gene constraint: LOEUF 0.694 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 53.52
Residue 89: the set domain

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-pro89ser (accessed [today's date]).

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