Is PRDM9 p.Tyr636Phe (c.1907A>T) pathogenic?

PRDM9 p.Tyr636Phe (c.1907A>T) is classified Likely benign in PRDM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-01). AlphaMissense: likely benign (0.2732); Rare (popmax 0.349%, sas).

How common is PRDM9 p.Tyr636Phe (c.1907A>T) in the general population?

PRDM9 p.Tyr636Phe (c.1907A>T) is rare (popmax 0.349%, sas) (gnomAD).

What do computational predictors say about PRDM9 p.Tyr636Phe (c.1907A>T)?

AlphaMissense predicts likely benign (score 0.2732) — an in-silico prediction, not a clinical call.

PRDM9 p.Tyr636Phe

c.1907A>T · VCV3388003

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2732 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.349%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2732	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -11.83	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -3.5
Regional constraint	o/e 0.00	constrained · MANE · 41 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	14.42	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 0.349% South Asian · 275/78,892 alleles

Filtering AF 0.315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.302%

Overall 0.265% 3,574/1,346,758 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.349%	287
Remaining individualsnot grpmax-eligible	0.343%	292
Admixed American	0.337%	297
European (non-Finnish)	0.278%	360
Finnishnot grpmax-eligible	0.232%	432
Ashkenazi Jewishnot grpmax-eligible	0.153%	653
Middle Eastern	0.143%	699
African / African-American	0.0868%	1,152

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.Tyr636Phe
Coding: c.1907A>T
MANE Select: NM_020227
Type: single nucleotide variant
Location: chr5:23526995 (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 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-tyr636phe (accessed [today's date]).

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