Is FANCD2 p.Ser784Phe (c.2351C>T) pathogenic?

FANCD2 p.Ser784Phe (c.2351C>T) is classified Conflicting classifications of pathogenicity in FANCD2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.2944); Very rare (popmax 0.00891%, eas); Associated with Fanconi anemia.

What condition is associated with FANCD2 p.Ser784Phe (c.2351C>T)?

FANCD2 p.Ser784Phe (c.2351C>T) is associated with Fanconi anemia, ovarian cancer, Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Ser784Phe (c.2351C>T) in the general population?

FANCD2 p.Ser784Phe (c.2351C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

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

What do computational predictors say about FANCD2 p.Ser784Phe (c.2351C>T)?

AlphaMissense predicts likely benign (score 0.2944) — an in-silico prediction, not a clinical call.

FANCD2 p.Ser784Phe

c.2351C>T · rs1398046806 · VCV1026310

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.2944	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -13.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 36 kb · p 0.0049 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00062% 10/1,612,572 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.0032%	31,215
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00133%	74,914
European (non-Finnish)	0.00017%	589,359

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.Ser784Phe
Coding: c.2351C>T
MANE Select: NM_001018115
dbSNP: rs1398046806
Type: single nucleotide variant
Location: chr3:10065945 (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 784: an α-helix

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

Disease context

Fanconi anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer Fanconi anemia complementation group D2

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

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-ser784phe (accessed [today's date]).

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