Is POLQ p.Cys99= (c.297C>T) pathogenic?

POLQ p.Cys99= (c.297C>T) is classified Likely benign in POLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-23). Ultra-rare (popmax 0.0165%, mid).

How common is POLQ p.Cys99= (c.297C>T) in the general population?

POLQ p.Cys99= (c.297C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

POLQ p.Cys99=

c.297C>T · rs1268818323 · VCV1798376

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 0.2	GERP -1.3, phastCons 0.79
Overall
CADD	7.476	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Overall 6.2e-05% 1/1,613,380 alleles · ultra-rare exomes 1/1,461,138 · genomes 0/152,242 · 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: POLQ
Protein: p.Cys99=
Coding: c.297C>T
MANE Select: NM_199420
dbSNP: rs1268818323
Type: single nucleotide variant
Location: chr3:121544773 (GRCh38)
Structure: AlphaFold pLDDT 70.62 · 19 PDB

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

Similar variants

POLQ p.Cys99Arg 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-cys99 (accessed [today's date]).

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