Is PRDM9 p.Ser814Arg (c.2442C>A) pathogenic?

PRDM9 p.Ser814Arg (c.2442C>A) is classified Likely benign in PRDM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: ambiguous (0.5061); Rare (popmax 0.364%, afr).

How common is PRDM9 p.Ser814Arg (c.2442C>A) in the general population?

PRDM9 p.Ser814Arg (c.2442C>A) is rare (popmax 0.364%, afr) (gnomAD).

What do computational predictors say about PRDM9 p.Ser814Arg (c.2442C>A)?

AlphaMissense predicts ambiguous (score 0.5061) — an in-silico prediction, not a clinical call.

PRDM9 p.Ser814Arg

c.2442C>A · VCV3388168

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5061 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.364%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5061	ambiguous
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Regional constraint	o/e 0.50	unconstrained · MANE · 567 bp · p 6.1e-12 · regional, not allelic
Overall
CADD	0.017	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 0.364% African / African-American · 192/52,802 alleles

Filtering AF 0.321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.305%

Overall 0.0433% 665/1,536,846 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.364%	275
East Asian	0.177%	564
Middle Eastern	0.162%	618
Remaining individualsnot grpmax-eligible	0.117%	857
Ashkenazi Jewishnot grpmax-eligible	0.112%	891
Admixed American	0.0838%	1,194
South Asian	0.0288%	3,468
European (non-Finnish)	0.019%	5,250
Finnishnot grpmax-eligible	0.00335%	29,894

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: PRDM9
Protein: p.Ser814Arg
Coding: c.2442C>A
MANE Select: NM_020227
Type: single nucleotide variant
Location: chr5:23527530 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.19 · 5 PDB
Residue 814: a β-strand; the 'dna-binding' region; a UniProt-annotated variant site (in allele l13; increases affinity for the dna-binding motif 5'-gcctccctagccacg-3' and)

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

Similar variants

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
PRDM9 p.Gly144= 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-ser814arg (accessed [today's date]).

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