Is POLQ p.Arg705Ser (c.2115A>C) pathogenic?

POLQ p.Arg705Ser (c.2115A>C) is classified Uncertain significance in POLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-20). AlphaMissense: ambiguous (0.5464); Absent from gnomAD v4.1.

How common is POLQ p.Arg705Ser (c.2115A>C) in the general population?

POLQ p.Arg705Ser (c.2115A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about POLQ p.Arg705Ser (c.2115A>C)?

AlphaMissense predicts ambiguous (score 0.5464) — an in-silico prediction, not a clinical call.

POLQ p.Arg705Ser

c.2115A>C · rs2546794675 · VCV1786160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5464 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5464	ambiguous
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.39	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 1.9, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: POLQ
Protein: p.Arg705Ser
Coding: c.2115A>C
MANE Select: NM_016218 · reported on NM_199420
dbSNP: rs2546794675
Type: single nucleotide variant
Location: chr3:121498515 (GRCh38)
Structure: AlphaFold pLDDT 70.62 · 19 PDB

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

Similar variants

POLK p.Asp705Ala Uncertain significance ★ ⚠ same residue
POLQ p.Arg705Gly Uncertain significance ★ ⚠ same residue
POLQ p.Arg705Lys Uncertain significance ★ ⚠ same residue
POLQ p.Arg705= Likely benign ★ 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

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-arg705ser (accessed [today's date]).

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