Is PRDM16 p.Arg2Pro (c.5G>C) pathogenic?

PRDM16 p.Arg2Pro (c.5G>C) is classified Uncertain significance in PRDM16 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely pathogenic (0.9316); Absent from gnomAD v4.1.

How common is PRDM16 p.Arg2Pro (c.5G>C) in the general population?

PRDM16 p.Arg2Pro (c.5G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDM16 p.Arg2Pro (c.5G>C)?

AlphaMissense predicts likely pathogenic (score 0.9316) — an in-silico prediction, not a clinical call.

PRDM16 p.Arg2Pro

c.5G>C · VCV3336933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9316 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9316	likely pathogenic
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 336 kb · p 0.018 · regional, not allelic
Overall
CADD	24.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRDM16
Protein: p.Arg2Pro
Coding: c.5G>C
MANE Select: NM_022114
Type: single nucleotide variant
Location: chr1:3069264 (GRCh38)
Gene constraint: LOEUF 0.304 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.73 · 2 PDB
Residue 2: the 'disordered' region

Full PRDM16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDM16 p.Arg2Gln Uncertain significance ★★ ⚠ same residue
PRDM16 c.388-2A>G Uncertain significance ★★ same type
PRDM16 p.Ala1035Ser Uncertain significance ★★ ⚠ same type
PRDM16 p.Ala106Thr Uncertain significance ★★ ⚠ same type
PRDM16 p.Ala1096Thr Uncertain significance ★★ ⚠ same type
PRDM16 p.Ala1096Val Uncertain significance ★★ ⚠ same type
PRDM16 p.Ala1146Thr Uncertain significance ★★ ⚠ same type
PRDM16 p.Ala175Val 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/prdm16-p-arg2pro (accessed [today's date]).

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