Is PALB2 p.Val627= (c.1881G>T) pathogenic?

PALB2 p.Val627= (c.1881G>T) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00144%, nfe); Associated with Breast and/or ovarian cancer.

What condition is associated with PALB2 p.Val627= (c.1881G>T)?

PALB2 p.Val627= (c.1881G>T) is associated with Breast and/or ovarian cancer, colon carcinoma, endometrial carcinoma (ClinVar).

How common is PALB2 p.Val627= (c.1881G>T) in the general population?

PALB2 p.Val627= (c.1881G>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

PALB2 p.Val627=

c.1881G>T · rs139362268 · VCV126626

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Conditions

Breast and/or ovarian cancer

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 0.12	GERP 0.9, phastCons 0.94
Overall
CADD	5.516	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,026 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00917% 148/1,614,046 alleles · very rare exomes 134/1,461,878 · genomes 14/152,168 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.382%	262
Remaining individualsnot grpmax-eligible	0.0288%	3,472
European (non-Finnish)grpmax	0.00144%	69,413

Ashkenazi Jewish 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.Val627=
Coding: c.1881G>T
MANE Select: NM_024675
dbSNP: rs139362268
Type: single nucleotide variant
Location: chr16:23630273 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 627: a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5); an α-helix

Full PALB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Breast and/or ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colon carcinoma endometrial carcinoma Fanconi anemia complementation group N pancreatic cancer, susceptibility to, 3 hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

PALB2 p.Val627Ala Uncertain significance ★★ ⚠ same residue
PALB2 p.Val627Gly Uncertain significance ★★ ⚠ same residue
PALB2 p.Val627Met Uncertain significance ★★ ⚠ same residue
PALB2 p.Val627Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Val627fs Pathogenic/Likely pathogenic ★★ 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-val627 (accessed [today's date]).

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