Is POLQ p.Pro291= (c.873G>A) pathogenic?

POLQ p.Pro291= (c.873G>A) is classified Benign in POLQ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-02-28). Common (popmax 6.24%, afr) — too common for a highly-penetrant pathogenic allele.

POLQ p.Pro291=

Q: How common is POLQ p.Pro291= (c.873G>A) in the general population?

POLQ p.Pro291= (c.873G>A) is common (popmax 6.24%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.873G>A · rs41390550 · VCV712466

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.24%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -2.6
Overall
CADD	6.381	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.24% African / African-American · 4,678/74,966 alleles

Filtering AF 6.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.03%

Overall 0.342% 5,521/1,613,760 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.24%	16
Admixed American	0.415%	241
Remaining individualsnot grpmax-eligible	0.371%	269
Middle Eastern	0.248%	404
European (non-Finnish)	0.0275%	3,642
East Asian	0.0201%	4,986
South Asian	0.0143%	7,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596

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: POLQ
Protein: p.Pro291=
Coding: c.873G>A
MANE Select: NM_016218 · reported on NM_199420
dbSNP: rs41390550
Type: single nucleotide variant
Location: chr3:121533077 (GRCh38)
Structure: AlphaFold pLDDT 70.62 · 19 PDB
Residue 291: the umuc domain; an α-helix

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

Similar variants

POLQ p.Pro291Ser Uncertain significance ★ same residue
POLQ p.Arg2169Cys Uncertain significance ★★ ⚠ same type
POLQ p.Arg2347Cys Uncertain significance ★★ ⚠ same type
POLQ p.Cys2219Tyr Uncertain significance ★★ ⚠ same type
POLQ p.Glu2246Lys Uncertain significance ★★ ⚠ same type
POLQ p.Glu731Ala Uncertain significance ★★ ⚠ same type
POLQ p.Lys68Glu Uncertain significance ★★ ⚠ same type
POLQ p.Met1707Val 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/polq-p-pro291 (accessed [today's date]).

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