Is FANCD2 p.Val379= (c.1137G>T) pathogenic?

FANCD2 p.Val379= (c.1137G>T) is classified Benign in FANCD2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-10). Common (popmax 39.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with FANCD2 p.Val379= (c.1137G>T)?

FANCD2 p.Val379= (c.1137G>T) is associated with hereditary breast ovarian cancer syndrome, Fanconi anemia complementation group D2, Fanconi anemia complementation group A (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.Val379=

Q: How common is FANCD2 p.Val379= (c.1137G>T) in the general population?

FANCD2 p.Val379= (c.1137G>T) is common (popmax 39.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1137G>T · rs72492997 · VCV342260

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 39.7%, 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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.073	GERP -2, phastCons 0.009
Overall
CADD	9.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39.7% African / African-American · 20,614/51,904 alleles

Filtering AF 39.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.1%

Overall 22.2% 194,681/875,606 alleles · common exomes 138,739/749,832 · genomes 55,942/125,774 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	43%	2
Finnishnot grpmax-eligible	40.6%	2
African / African-Americangrpmax	39.7%	3
Middle Eastern	31.5%	3
Ashkenazi Jewishnot grpmax-eligible	29.1%	3
East Asian	25.5%	4
Remaining individualsnot grpmax-eligible	23.8%	4
Admixed American	23.1%	4
European (non-Finnish)	19.8%	5
South Asian	10.2%	10

Amish 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: FANCD2
Protein: p.Val379=
Coding: c.1137G>T
MANE Select: NM_001018115
dbSNP: rs72492997
Type: single nucleotide variant
Location: chr3:10046582 (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 379: 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 complementation group A Fanconi anemia

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

FANCD2 p.Val379Ala Uncertain significance ★ ⚠ same residue
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

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-val379 (accessed [today's date]).

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