Is POLG2 p.Phe439= (c.1317C>T) pathogenic?

POLG2 p.Phe439= (c.1317C>T) is classified Likely benign in POLG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). Very rare (popmax 0.00667%, afr).

How common is POLG2 p.Phe439= (c.1317C>T) in the general population?

POLG2 p.Phe439= (c.1317C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

POLG2 p.Phe439=

c.1317C>T · rs372118103 · VCV1663513

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

⚠ 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
Pangolin	Δ0.31	loss · gain 0.23 · independent
Constraint at this position
Conservation	phyloP 5	GERP 0.49, phastCons 1
Overall
CADD	16.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% African / African-American · 5/74,916 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00031% 5/1,613,780 alleles · very rare exomes 3/1,461,628 · genomes 2/152,152 · joint denominator

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.Phe439=
Coding: c.1317C>T
MANE Select: NM_007215
dbSNP: rs372118103
Type: single nucleotide variant
Location: chr17:64477964 (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-phe439 (accessed [today's date]).

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