Is POLD1 p.Phe970= (c.2910C>T) pathogenic?

POLD1 p.Phe970= (c.2910C>T) is classified Likely benign in POLD1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-29). Very rare (popmax 0.0039%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with POLD1 p.Phe970= (c.2910C>T)?

POLD1 p.Phe970= (c.2910C>T) is associated with hereditary neoplastic syndrome, POLD1-related polyposis and colorectal cancer syndrome (ClinVar).

How common is POLD1 p.Phe970= (c.2910C>T) in the general population?

POLD1 p.Phe970= (c.2910C>T) is very rare (popmax 0.0039%, amr) (gnomAD).

POLD1 p.Phe970=

c.2910C>T · rs757740787 · VCV239318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0039%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.621	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.6	GERP -2.4
Overall
CADD	5.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% Admixed American · 2/51,292 alleles

Filtering AF 0.00213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00188%

Overall 0.00251% 39/1,551,748 alleles · very rare exomes 34/1,399,532 · genomes 5/152,216 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0039%	25,646
European (non-Finnish)	0.00296%	33,775
South Asian	0.00237%	42,121
African / African-American	0.00137%	73,158

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: POLD1
Protein: p.Phe970=
Coding: c.2910C>T
MANE Select: NM_002691
dbSNP: rs757740787
Type: single nucleotide variant
Location: chr19:50416485 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 6 PDB
Residue 970: an α-helix

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

Also linked: POLD1-related polyposis and colorectal cancer syndrome

Similar variants

POLD1 p.Phe970Leu Uncertain significance ★★ ⚠ same residue
POLD1 p.Phe970Ser Uncertain significance ★ ⚠ same residue
POLD1 p.Arg507Cys Likely pathogenic ★★ same condition
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>A 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-phe970 (accessed [today's date]).

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