Is POLD1 p.Pro71= (c.213A>C) pathogenic?

POLD1 p.Pro71= (c.213A>C) is classified Likely benign in POLD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with POLD1 p.Pro71= (c.213A>C)?

POLD1 p.Pro71= (c.213A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is POLD1 p.Pro71= (c.213A>C) in the general population?

POLD1 p.Pro71= (c.213A>C) is absent from gnomAD v4.1 (gnomAD).

POLD1 p.Pro71=

c.213A>C · rs112721361 · VCV1786530

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.77	GERP -1.8
Overall
CADD	2.933	PHRED · no single calibrated threshold — expert panels disagree

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: POLD1
Protein: p.Pro71=
Coding: c.213A>C
MANE Select: NM_002691
dbSNP: rs112721361
Type: single nucleotide variant
Location: chr19:50399381 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 6 PDB

Full POLD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POLD1 p.Pro71Leu Uncertain significance ★★ ⚠ same residue
POLD1 p.Leu474Pro Pathogenic/Likely pathogenic ★★ same condition
POLD1 p.Ser478Asn Pathogenic/Likely pathogenic ★★ same condition
POLD1 c.1137+1G>A Uncertain significance ★★ same condition
POLD1 c.1137+3A>G Uncertain significance ★★ same condition
POLD1 c.1383+1G>C Uncertain significance ★★ same condition
POLD1 c.1383+1G>T Uncertain significance ★★ same condition
POLD1 c.1383+4T>C Uncertain significance ★★ same condition

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/pold1-p-pro71 (accessed [today's date]).

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