Is POLG2 p.Arg225= (c.673C>A) pathogenic?

POLG2 p.Arg225= (c.673C>A) is classified Likely benign in POLG2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-27). Very rare (popmax 0.00831%, nfe).

How common is POLG2 p.Arg225= (c.673C>A) in the general population?

POLG2 p.Arg225= (c.673C>A) is very rare (popmax 0.00831%, nfe) (gnomAD).

POLG2 p.Arg225=

c.673C>A · rs371515325 · VCV1990504

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00831%, 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 0.11	GERP -1.2
Overall
CADD	1.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00831% European (non-Finnish) · 98/1,179,914 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00632% 102/1,613,752 alleles · very rare exomes 93/1,461,746 · genomes 9/152,006 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,040
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,414

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.Arg225=
Coding: c.673C>A
MANE Select: NM_007215
dbSNP: rs371515325
Type: single nucleotide variant
Location: chr17:64492911 (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-arg225 (accessed [today's date]).

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