Is FANCD2 p.Ser390= (c.1170C>T) pathogenic?

FANCD2 p.Ser390= (c.1170C>T) is classified Benign/Likely benign in FANCD2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-23). Common (popmax 45.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with FANCD2 p.Ser390= (c.1170C>T)?

FANCD2 p.Ser390= (c.1170C>T) is associated with hereditary breast ovarian cancer syndrome, Fanconi anemia complementation group D2, Fanconi anemia (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

FANCD2 p.Ser390=

Q: How common is FANCD2 p.Ser390= (c.1170C>T) in the general population?

FANCD2 p.Ser390= (c.1170C>T) is common (popmax 45.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1170C>T · rs112887807 · VCV342261

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 45.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary breast ovarian cancer syndrome

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 · C>G here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 1
Overall
CADD	12.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 45.7% African / African-American · 26,022/56,912 alleles

Filtering AF 45.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 45.1%

Overall 37.8% 360,481/954,076 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	45.7%	2
Finnishnot grpmax-eligible	44.5%	2
Amishnot grpmax-eligible	43.9%	2
Middle Eastern	40.5%	2
Ashkenazi Jewishnot grpmax-eligible	39.1%	3
European (non-Finnish)	38.1%	3
Remaining individualsnot grpmax-eligible	38.1%	3
East Asian	32%	3
Admixed American	31.5%	3
South Asian	23.5%	4

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: FANCD2
Protein: p.Ser390=
Coding: c.1170C>T
MANE Select: NM_001018115
dbSNP: rs112887807
Type: single nucleotide variant
Location: chr3:10046615 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.24 · 13 PDB
Residue 390: an α-helix

Full FANCD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group D2 Fanconi anemia

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

FANCD2 c.1279-1G>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.1279-2A>G Likely pathogenic ★★ same condition
FANCD2 c.1948-16T>G Pathogenic ★★ same condition
FANCD2 c.1948-6C>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.206-1G>T Likely pathogenic ★★ same condition
FANCD2 c.2169-1G>C Likely pathogenic ★★ same condition
FANCD2 c.2269+1G>A Likely pathogenic ★★ same condition
FANCD2 c.2715+1G>A Pathogenic/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/fancd2-p-ser390 (accessed [today's date]).

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