Is FANCD2 p.Asp184= (c.552C>T) pathogenic?

FANCD2 p.Asp184= (c.552C>T) is classified Conflicting classifications of pathogenicity in FANCD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-12). Very rare (popmax 0.00133%, afr); Associated with Fanconi anemia complementation group D2.

What condition is associated with FANCD2 p.Asp184= (c.552C>T)?

FANCD2 p.Asp184= (c.552C>T) is associated with Fanconi anemia complementation group D2, Fanconi anemia (ClinVar).

How common is FANCD2 p.Asp184= (c.552C>T) in the general population?

FANCD2 p.Asp184= (c.552C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

FANCD2 p.Asp184=

c.552C>T · rs2086806957 · VCV899815

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Fanconi anemia complementation group D2

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 0.088	GERP 0.038, phastCons 0.93
Overall
CADD	8.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,916 alleles

Overall 0.000124% 2/1,613,418 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,916
European (non-Finnish)	8.48e-05%	1,179,523

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.Asp184=
Coding: c.552C>T
MANE Select: NM_001018115
dbSNP: rs2086806957
Type: single nucleotide variant
Location: chr3:10039339 (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 184: the 'interaction with fance' region

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

Disease context

Fanconi anemia complementation group D2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia

Similar variants

FANCD2 p.Asp184Ala Uncertain significance ★ ⚠ same residue
FANCD2 p.Asp184Tyr 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

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-asp184 (accessed [today's date]).

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