Is POLG2 p.Phe354= (c.1062C>T) pathogenic?

POLG2 p.Phe354= (c.1062C>T) is classified Likely benign in POLG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-09). Ultra-rare (popmax 0.0164%, mid).

How common is POLG2 p.Phe354= (c.1062C>T) in the general population?

POLG2 p.Phe354= (c.1062C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

POLG2 p.Phe354=

c.1062C>T · rs782024394 · VCV1661485

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

⚠ 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 2.2	GERP -0.029, phastCons 1
Overall
CADD	6.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00155% 25/1,612,758 alleles · ultra-rare exomes 24/1,460,580 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00641%	15,612
East Asian	0.00223%	44,888
European (non-Finnish)	0.00153%	65,491
South Asian	0.0011%	91,050

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.Phe354=
Coding: c.1062C>T
MANE Select: NM_007215
dbSNP: rs782024394
Type: single nucleotide variant
Location: chr17:64485776 (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-phe354 (accessed [today's date]).

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