Is PALB2 p.His69= (c.207C>T) pathogenic?

PALB2 p.His69= (c.207C>T) is classified Likely benign in PALB2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-11-13). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.His69= (c.207C>T)?

PALB2 p.His69= (c.207C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.His69= (c.207C>T) in the general population?

PALB2 p.His69= (c.207C>T) is absent from gnomAD v4.1 (gnomAD).

PALB2 p.His69=

c.207C>T · rs1567223897 · VCV830093

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.8, phastCons 0.62
Overall
CADD	1.939	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: PALB2
Protein: p.His69=
Coding: c.207C>T
MANE Select: NM_024675
dbSNP: rs1567223897
Type: single nucleotide variant
Location: chr16:23637854 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 69: the 'interaction with rad51' region; the 'required for its oligomerization and is important for its focal concentration at dna damage sites' region; the 'disordered' region; the 'dna-binding (with the preference d loop > dsdna > ssdna)' region; the 'interaction with brca1' region

Full PALB2 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

PALB2 p.His69Arg Uncertain significance ★★ ⚠ same residue
PALB2 p.His69Gln Uncertain significance ★★ ⚠ same residue
PALB2 p.His69Pro Uncertain significance ★★ ⚠ same residue
PALB2 p.His69Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.His69Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys Pathogenic ★★★ ⚠ same condition
PALB2 p.Gln228Ter Pathogenic ★★★ 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/palb2-p-his69 (accessed [today's date]).

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