Is POLQ p.Asp995= (c.2985T>C) pathogenic?

POLQ p.Asp995= (c.2985T>C) is classified Likely benign in POLQ (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-19). Very rare (popmax 0.00894%, eas).

How common is POLQ p.Asp995= (c.2985T>C) in the general population?

POLQ p.Asp995= (c.2985T>C) is very rare (popmax 0.00894%, eas) (gnomAD).

POLQ p.Asp995=

c.2985T>C · rs1169776545 · VCV1798437

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00894%, eas)

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 0.93	GERP -3.4
Overall
CADD	2.556	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00894% East Asian · 4/44,766 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000253% 4/1,580,008 alleles · very rare exomes 4/1,427,720 · genomes 0/152,288 · 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.Asp995=
Coding: c.2985T>C
MANE Select: NM_199420
dbSNP: rs1169776545
Type: single nucleotide variant
Location: chr3:121489946 (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.Asp995Gly Uncertain significance ★ ⚠ same residue
POLQ p.Asp995His 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-asp995 (accessed [today's date]).

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