Is PALB2 p.Val836= (c.2508C>G) pathogenic?

PALB2 p.Val836= (c.2508C>G) is classified Benign/Likely benign in PALB2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). Very rare (popmax 0.00333%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with PALB2 p.Val836= (c.2508C>G)?

PALB2 p.Val836= (c.2508C>G) is associated with hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is PALB2 p.Val836= (c.2508C>G) in the general population?

PALB2 p.Val836= (c.2508C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

PALB2 p.Val836=

c.2508C>G · rs786203603 · VCV187271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -0.28	GERP -3.7
Overall
CADD	0.271	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,986 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,700 alleles · very rare exomes 5/1,461,526 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,993
African / African-American	0.00133%	74,908
South Asian	0.0011%	91,056
European (non-Finnish)	0.000254%	393,284

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.Val836=
Coding: c.2508C>G
MANE Select: NM_024675
dbSNP: rs786203603
Type: single nucleotide variant
Location: chr16:23629646 (GRCh38)
Gene constraint: LOEUF 0.9 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.07 · 4 PDB
Residue 836: the 'required for interaction with polh and polh dna synthesis stimulation' region; a UniProt-annotated variant site (risk factor for brovca5); a UniProt-annotated variant site (in fancn; risk factor for brovca5)

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

Also linked: hereditary breast carcinoma

Similar variants

PALB2 p.Val836Asp Uncertain significance ★★ ⚠ same residue
PALB2 p.Val836Ala Uncertain significance ★ ⚠ same residue
PALB2 p.Val836Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Val836Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Val836Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
PALB2 p.Val836fs Pathogenic ★ same residue
PALB2 p.Val836del Conflicting classifications of pathogenicity ★ same residue
PALB2 c.3350+4A>G Likely 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-val836 (accessed [today's date]).

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