Is POLQ p.Ala249= (c.747A>C) pathogenic?

POLQ p.Ala249= (c.747A>C) is classified Likely benign in POLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-16). Very rare (popmax 0.00138%, afr).

How common is POLQ p.Ala249= (c.747A>C) in the general population?

POLQ p.Ala249= (c.747A>C) is very rare (popmax 0.00138%, afr) (gnomAD).

POLQ p.Ala249=

c.747A>C · rs2048424966 · VCV1759084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00138%, afr)

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 1.5	GERP 0.55, phastCons 0.73
Overall
CADD	6.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00138% African / African-American · 1/72,588 alleles

Overall 7.11e-05% 1/1,405,920 alleles · very rare

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.Ala249=
Coding: c.747A>C
MANE Select: NM_199420
dbSNP: rs2048424966
Type: single nucleotide variant
Location: chr3:121533203 (GRCh38)
Structure: AlphaFold pLDDT 70.62 · 19 PDB
Residue 249: the umuc domain; an α-helix

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

Similar variants

POLQ p.Ala249Ser Uncertain significance ★ ⚠ same residue
POLQ p.Ala249Thr 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

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-ala249 (accessed [today's date]).

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