Is FANCD2 p.Phe708= (c.2124T>C) pathogenic?

FANCD2 p.Phe708= (c.2124T>C) is classified Benign in FANCD2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 8.78%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with FANCD2 p.Phe708= (c.2124T>C)?

FANCD2 p.Phe708= (c.2124T>C) 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.Phe708=

Q: How common is FANCD2 p.Phe708= (c.2124T>C) in the general population?

FANCD2 p.Phe708= (c.2124T>C) is common (popmax 8.78%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2124T>C · rs9809716 · VCV257072

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 8.78%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -3.7, phastCons 0.019
Overall
CADD	5.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.78% African / African-American · 6,580/74,904 alleles

Filtering AF 8.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.53%

Overall 0.462% 7,461/1,613,774 alleles · common exomes 3,574/1,461,550 · genomes 3,887/152,224 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.78%	11
Remaining individualsnot grpmax-eligible	0.6%	167
Admixed American	0.542%	185
Middle Eastern	0.231%	432
European (non-Finnish)	0.0136%	7,328
South Asian	0.00549%	18,216
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Phe708=
Coding: c.2124T>C
MANE Select: NM_001018115
dbSNP: rs9809716
Type: single nucleotide variant
Location: chr3:10064831 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.24 · 13 PDB

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-phe708 (accessed [today's date]).

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