Is PALB2 p.Ser10= (c.30C>T) pathogenic?

PALB2 p.Ser10= (c.30C>T) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-09). Very rare (popmax 0.00017%, nfe); Associated with hereditary breast carcinoma.

What condition is associated with PALB2 p.Ser10= (c.30C>T)?

PALB2 p.Ser10= (c.30C>T) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Ser10= (c.30C>T) in the general population?

PALB2 p.Ser10= (c.30C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

PALB2 p.Ser10=

c.30C>T · rs758500749 · VCV822895

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 0.71, phastCons 1
Overall
CADD	15.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,880 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,428 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,420
European (non-Finnish)grpmax	0.00017%	589,939

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PALB2
Protein: p.Ser10=
Coding: c.30C>T
MANE Select: NM_024675
dbSNP: rs758500749
Type: single nucleotide variant
Location: chr16:23641128 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 10: the 'interaction with rad51' region; the 'required for its oligomerization and is important for its focal concentration at dna damage sites' 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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

PALB2 p.Ser10Ile Uncertain significance ★★ ⚠ same residue
PALB2 p.Ser10Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Ser10Asn Uncertain significance ★ ⚠ same residue
PALB2 p.Ser10Cys Uncertain significance ★ ⚠ same residue
PALB2 p.Ser10Gly Uncertain significance ★ ⚠ same residue
PALB2 p.Ser10Thr Uncertain significance ★ ⚠ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys 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-ser10 (accessed [today's date]).

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