Is FANCD2 p.Ser441fs (c.1321_1322del) pathogenic?

FANCD2 p.Ser441fs (c.13211322del) is classified Uncertain significance in FANCD2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-11). Very rare (popmax 8.47e-05%, nfe); Associated with Fanconi anemia complementation group D2.

What condition is associated with FANCD2 p.Ser441fs (c.1321_1322del)?

FANCD2 p.Ser441fs (c.1321_1322del) is associated with Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Ser441fs (c.1321_1322del) in the general population?

FANCD2 p.Ser441fs (c.1321_1322del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

FANCD2 p.Ser441fs

c.1321_1322del · rs2087073639 · VCV929654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Fanconi anemia complementation group D2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,054 alleles

Overall 6.2e-05% 1/1,613,688 alleles · very rare exomes 1/1,461,272 · genomes 0/152,416 · joint denominator

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.Ser441fs
Coding: c.1321_1322del
MANE Select: NM_001018115
dbSNP: rs2087073639
Type: Microsatellite
Location: chr3:10047957 (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 441: an α-helix

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

Similar variants

FANCD2 c.3107_3108del Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Ala629fs Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Leu700del Uncertain significance ★★ same condition
FANCD2 p.Glu63fs Likely pathogenic ★ same condition
FANCD2 p.Lys865fs Likely pathogenic ★ same condition
FANCD2 p.Ser272del Uncertain significance ★ same condition
FANCD2 c.1279-1G>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.1279-2A>G 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-ser441fs (accessed [today's date]).

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