Is PRDM6 p.Pro65Arg (c.194C>G) pathogenic?

PRDM6 p.Pro65Arg (c.194C>G) is classified Uncertain significance in PRDM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.1552); Ultra-rare (popmax 0.015%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRDM6 p.Pro65Arg (c.194C>G)?

PRDM6 p.Pro65Arg (c.194C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRDM6 p.Pro65Arg (c.194C>G) in the general population?

PRDM6 p.Pro65Arg (c.194C>G) is ultra-rare (popmax 0.015%, eas) (gnomAD).

What do computational predictors say about PRDM6 p.Pro65Arg (c.194C>G)?

AlphaMissense predicts likely benign (score 0.1552) — an in-silico prediction, not a clinical call.

PRDM6 p.Pro65Arg

c.194C>G · VCV3309816

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1552 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1552	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.75	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 0.067	GERP -0.16
Regional constraint	o/e 1.13	unconstrained · MANE · 81 kb · p 0.0014 · regional, not allelic
Overall
CADD	15.6	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 0.015% East Asian · 5/33,326 alleles

Filtering AF 0.00587% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.000473% 7/1,481,304 alleles · ultra-rare exomes 5/1,329,524 · genomes 2/151,780 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.015%	6,665
Admixed American	0.00235%	42,508
European (non-Finnish)	8.94e-05%	1,118,678

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.Pro65Arg
Coding: c.194C>G
MANE Select: NM_001136239
Type: single nucleotide variant
Location: chr5:123090208 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI 0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 57.72
Residue 65: 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.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
PRDM6 p.Ala141Thr Uncertain significance ★ ⚠ same condition
PRDM6 p.Ala232Thr 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-pro65arg (accessed [today's date]).

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