Is PRDM6 p.Pro47Arg (c.140C>G) pathogenic?

PRDM6 p.Pro47Arg (c.140C>G) is classified Likely benign in PRDM6 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-14). AlphaMissense: likely benign (0.1726); Rare (popmax 0.17%, nfe).

How common is PRDM6 p.Pro47Arg (c.140C>G) in the general population?

PRDM6 p.Pro47Arg (c.140C>G) is rare (popmax 0.17%, nfe) (gnomAD).

What do computational predictors say about PRDM6 p.Pro47Arg (c.140C>G)?

AlphaMissense predicts likely benign (score 0.1726) — an in-silico prediction, not a clinical call.

PRDM6 p.Pro47Arg

c.140C>G · VCV3356848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1726 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.17%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1726	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -8.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP -0.24, phastCons 0.95
Regional constraint	o/e 1.13	unconstrained · MANE · 81 kb · p 0.0014 · regional, not allelic
Overall
CADD	14.65	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 0.17% European (non-Finnish) · 1,931/1,135,462 alleles

Filtering AF 0.164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.161%

Overall 0.137% 2,083/1,521,304 alleles · rare exomes 1,938/1,369,228 · genomes 145/152,076 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.17%	588
Remaining individualsnot grpmax-eligible	0.155%	646
Admixed American	0.064%	1,562
African / African-American	0.0244%	4,092
Finnishnot grpmax-eligible	0.0211%	4,739
South Asian	0.00123%	81,604

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.Pro47Arg
Coding: c.140C>G
MANE Select: NM_001136239
Type: single nucleotide variant
Location: chr5:123090154 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 57.72
Residue 47: 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-pro47arg (accessed [today's date]).

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