Is PRDM6 p.Pro58fs (c.167_168insG) pathogenic?

PRDM6 p.Pro58fs (c.167168insG) is classified Benign in PRDM6 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 3.88%, afr).

How common is PRDM6 p.Pro58fs (c.167_168insG) in the general population?

PRDM6 p.Pro58fs (c.167_168insG) is low-frequency (popmax 3.88%, afr) (gnomAD).

PRDM6 p.Pro58fs

c.167_168insG · rs768810414 · VCV768029

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 3.88%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.4	GERP 0.63, phastCons 0.98
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.88% African / African-American · 2,633/67,844 alleles

Filtering AF 3.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.71%

Overall 0.196% 2,912/1,487,364 alleles · low-frequency exomes 1,220/1,335,428 · genomes 1,692/151,936 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.88%	26
Remaining individualsnot grpmax-eligible	0.231%	433
Admixed American	0.23%	436
Middle Eastern	0.129%	774
South Asian	0.00778%	12,848
European (non-Finnish)	0.00339%	29,541

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.Pro58fs
Coding: c.167_168insG
MANE Select: NM_001136239
dbSNP: rs768810414
Type: Insertion
Location: chr5:123090181 (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

Similar variants

PRDM6 p.Pro58_Pro59del Uncertain significance ★ same residue
PRDM6 p.Pro58Arg Uncertain significance ★ ⚠ same residue
PRDM6 p.Pro58Leu Uncertain significance ★ ⚠ same residue
PRDM6 p.Pro58= Likely benign ★ same residue

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-pro58fs (accessed [today's date]).

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