Is PRDM9 p.Pro635His (c.1904C>A) pathogenic?

PRDM9 p.Pro635His (c.1904C>A) is classified Uncertain significance in PRDM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely pathogenic (0.896); Absent from gnomAD v4.1.

How common is PRDM9 p.Pro635His (c.1904C>A) in the general population?

PRDM9 p.Pro635His (c.1904C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM9 p.Pro635His (c.1904C>A)?

AlphaMissense predicts likely pathogenic (score 0.896) — an in-silico prediction, not a clinical call.

PRDM9 p.Pro635His

c.1904C>A · VCV3424782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.896 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.896	likely pathogenic · top 9% in PRDM9
REVEL	0.114	moderately benign-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.87, phastCons 0.93
Regional constraint	o/e 0.00	constrained · MANE · 41 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	20.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM9
Protein: p.Pro635His
Coding: c.1904C>A
MANE Select: NM_020227
Type: single nucleotide variant
Location: chr5:23526992 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.19 · 5 PDB

Full PRDM9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM9 p.Pro635Ala Uncertain significance ★ ⚠ same residue
PRDM9 c.301+67A>G Benign ★★ same type
PRDM9 c.509-41C>T Benign ★★ same type
PRDM9 c.883-52C>T Benign ★★ same type
PRDM9 c.*125G>A Benign ★★ same type
PRDM9 c.*37A>G Benign ★★ same type
PRDM9 p.Asn790His Likely benign ★★ same type
PRDM9 p.Asp30= Benign ★★ 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/prdm9-p-pro635his (accessed [today's date]).

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