Is POLG2 p.Pro270= (c.810A>G) pathogenic?

POLG2 p.Pro270= (c.810A>G) is classified Likely benign in POLG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-10). Very rare (popmax 0.00568%, nfe).

How common is POLG2 p.Pro270= (c.810A>G) in the general population?

POLG2 p.Pro270= (c.810A>G) is very rare (popmax 0.00568%, nfe) (gnomAD).

POLG2 p.Pro270=

c.810A>G · rs782050886 · VCV721732

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -4	GERP -3.8
Overall
CADD	2.824	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00568% European (non-Finnish) · 67/1,179,548 alleles

Filtering AF 0.00454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.0044% 71/1,613,512 alleles · very rare exomes 67/1,461,312 · genomes 4/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,605
Admixed American	0.005%	20,002
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: POLG2
Protein: p.Pro270=
Coding: c.810A>G
MANE Select: NM_007215
dbSNP: rs782050886
Type: single nucleotide variant
Location: chr17:64490955 (GRCh38)

Full POLG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/polg2-p-pro270 (accessed [today's date]).

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