Is PALB2 p.Ser201= (c.603T>C) pathogenic?

PALB2 p.Ser201= (c.603T>C) is classified Likely benign in PALB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-28). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Ser201= (c.603T>C)?

PALB2 p.Ser201= (c.603T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is PALB2 p.Ser201= (c.603T>C) in the general population?

PALB2 p.Ser201= (c.603T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

PALB2 p.Ser201=

c.603T>C · rs769647912 · VCV1751238

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 3	GERP -0.81, phastCons 0.17
Overall
CADD	4.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,092 alleles

Overall 6.2e-05% 1/1,614,052 alleles · very rare exomes 0/1,461,876 · genomes 1/152,176 · 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: PALB2
Protein: p.Ser201=
Coding: c.603T>C
MANE Select: NM_024675
dbSNP: rs769647912
Type: single nucleotide variant
Location: chr16:23635943 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 201: 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.Ser201Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Ser201fs Pathogenic/Likely pathogenic ★★ same residue
PALB2 p.Ser201Arg Uncertain significance ★ ⚠ same residue
PALB2 c.3350+4A>G Likely pathogenic ★★★ same condition
PALB2 p.Arg1117Lys Pathogenic ★★★ ⚠ same condition
PALB2 p.Gln228Ter Pathogenic ★★★ same condition
PALB2 p.Gln692Ter Likely pathogenic ★★★ same condition
PALB2 p.Glu3Ter 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-ser201 (accessed [today's date]).

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