Is PRDM6 p.Pro58Arg (c.173C>G) pathogenic?

PRDM6 p.Pro58Arg (c.173C>G) is classified Uncertain significance in PRDM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.1388); Very rare (popmax 0.00468%, amr); Associated with Inborn genetic diseases.

What condition is associated with PRDM6 p.Pro58Arg (c.173C>G)?

PRDM6 p.Pro58Arg (c.173C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRDM6 p.Pro58Arg (c.173C>G) in the general population?

PRDM6 p.Pro58Arg (c.173C>G) is very rare (popmax 0.00468%, amr) (gnomAD).

What do computational predictors say about PRDM6 p.Pro58Arg (c.173C>G)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

PRDM6 p.Pro58Arg

c.173C>G · rs1159380796 · VCV2207720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00468%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -9.38	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 0.38	GERP -1.3, phastCons 0.033
Regional constraint	o/e 1.13	unconstrained · MANE · 81 kb · p 0.0014 · regional, not allelic
Overall
CADD	12.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00468% Admixed American · 2/42,776 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.00202% 30/1,488,140 alleles · very rare exomes 29/1,336,298 · genomes 1/151,842 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00468%	21,388
European (non-Finnish)	0.00241%	41,579
Remaining individualsnot grpmax-eligible	0.00175%	57,220

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.Pro58Arg
Coding: c.173C>G
MANE Select: NM_001136239
dbSNP: rs1159380796
Type: single nucleotide variant
Location: chr5:123090187 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 57.72
Residue 58: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDM6 p.Pro58Leu Uncertain significance ★ ⚠ same residue
PRDM6 p.Pro58= Likely benign ★ same residue
PRDM6 p.Leu26Phe Uncertain significance ★★ ⚠ same condition
PRDM6 p.Lys149Met Uncertain significance ★★ ⚠ same condition
PRDM6 p.Pro56= Likely benign ★★ same condition
PRDM6 p.Ala101Pro Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala102Pro Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala124Val Uncertain significance ★ ⚠ same condition

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-pro58arg (accessed [today's date]).

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