Is FANCD2 p.Val610= (c.1830G>A) pathogenic?

FANCD2 p.Val610= (c.1830G>A) is classified Conflicting classifications of pathogenicity in FANCD2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-11-27). Very rare (popmax 0.000339%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCD2 p.Val610= (c.1830G>A)?

FANCD2 p.Val610= (c.1830G>A) is associated with Fanconi anemia, Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Val610= (c.1830G>A) in the general population?

FANCD2 p.Val610= (c.1830G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

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

FANCD2 p.Val610=

c.1830G>A · rs1447943740 · VCV901484

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 0.000339%, nfe)

Conditions

Fanconi anemia

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 5	GERP 0.74, phastCons 1
Overall
CADD	12.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,046 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,874 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)grpmax	0.000339%	295,011

Remaining individuals 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.Val610=
Coding: c.1830G>A
MANE Select: NM_001018115
dbSNP: rs1447943740
Type: single nucleotide variant
Location: chr3:10063794 (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 610: 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: 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-val610 (accessed [today's date]).

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