Is POLQ p.Asp2414= (c.7242C>T) pathogenic?

POLQ p.Asp2414= (c.7242C>T) is classified Likely benign in POLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Rare (popmax 0.252%, afr).

How common is POLQ p.Asp2414= (c.7242C>T) in the general population?

POLQ p.Asp2414= (c.7242C>T) is rare (popmax 0.252%, afr) (gnomAD).

POLQ p.Asp2414=

c.7242C>T · rs140794457 · VCV1757875

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.252%, 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 0.13	GERP -1.2, phastCons 0.84
Overall
CADD	4.165	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.252% African / African-American · 186/73,932 alleles

Filtering AF 0.222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.211%

Overall 0.0127% 198/1,562,334 alleles · rare exomes 103/1,410,018 · genomes 95/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.252%	397
Remaining individualsnot grpmax-eligible	0.0115%	8,679
Admixed American	0.00501%	19,980
European (non-Finnish)	0.000177%	566,466

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.Asp2414=
Coding: c.7242C>T
MANE Select: NM_199420
dbSNP: rs140794457
Type: single nucleotide variant
Location: chr3:121449337 (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.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
POLQ p.Thr1010Ala 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-asp2414 (accessed [today's date]).

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