Is PRDM6 p.Pro64Ala (c.190C>G) pathogenic?

PRDM6 p.Pro64Ala (c.190C>G) is classified Likely benign in PRDM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.077); Rare (popmax 0.429%, mid).

How common is PRDM6 p.Pro64Ala (c.190C>G) in the general population?

PRDM6 p.Pro64Ala (c.190C>G) is rare (popmax 0.429%, mid) (gnomAD).

What do computational predictors say about PRDM6 p.Pro64Ala (c.190C>G)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

PRDM6 p.Pro64Ala

c.190C>G · VCV4971759

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.429%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.12	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 2.2	GERP 0.81, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 81 kb · p 0.0014 · regional, not allelic
Overall
CADD	15.59	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 0.429% Middle Eastern · 19/4,434 alleles

Filtering AF 0.337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.333%

Overall 0.314% 4,669/1,484,984 alleles · rare exomes 4,352/1,333,118 · genomes 317/151,866 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.429%	233
Finnishnot grpmax-eligible	0.407%	246
European (non-Finnish)	0.346%	289
South Asian	0.335%	298
Remaining individualsnot grpmax-eligible	0.286%	350
Admixed American	0.242%	413
African / African-American	0.044%	2,271
East Asian	0.00596%	16,768
Ashkenazi Jewishnot grpmax-eligible	0.00376%	26,616

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: PRDM6
Protein: p.Pro64Ala
Coding: c.190C>G
MANE Select: NM_001136239
Type: single nucleotide variant
Location: chr5:123090204 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 57.72
Residue 64: the 'disordered' region

Full PRDM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM6 p.Leu26Phe Uncertain significance ★★ ⚠ same type
PRDM6 p.Lys149Met Uncertain significance ★★ ⚠ same type
PRDM6 p.Ser78Cys Uncertain significance ★★ ⚠ same type
PRDM6 p.Cys503= Likely benign ★★ same type
PRDM6 p.Gly153= Likely benign ★★ same type
PRDM6 p.Pro56= Likely benign ★★ same type
PRDM6 p.Ala101Pro Uncertain significance ★ ⚠ same type
PRDM6 p.Ala102Pro 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/prdm6-p-pro64ala (accessed [today's date]).

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