Is FANCD2 p.Asp381= (c.1143C>T) pathogenic?

FANCD2 p.Asp381= (c.1143C>T) is classified Likely benign in FANCD2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-08-01). Rare (popmax 0.115%, mid); Associated with Fanconi anemia complementation group A.

What condition is associated with FANCD2 p.Asp381= (c.1143C>T)?

FANCD2 p.Asp381= (c.1143C>T) is associated with Fanconi anemia complementation group A, Fanconi anemia complementation group D2, Fanconi anemia (ClinVar).

How common is FANCD2 p.Asp381= (c.1143C>T) in the general population?

FANCD2 p.Asp381= (c.1143C>T) is rare (popmax 0.115%, mid) (gnomAD).

FANCD2 p.Asp381=

c.1143C>T · rs376349741 · VCV695992

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

Fanconi anemia complementation group A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.053	GERP -0.29, phastCons 0.002
Overall
CADD	6.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.0152% 246/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
African / African-American	0.0613%	1,632
Admixed American	0.0566%	1,766
Remaining individualsnot grpmax-eligible	0.0224%	4,465
European (non-Finnish)	0.012%	8,310
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Finnishnot grpmax-eligible	0.00312%	32,023

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.Asp381=
Coding: c.1143C>T
MANE Select: NM_001018115
dbSNP: rs376349741
Type: single nucleotide variant
Location: chr3:10046588 (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 381: an α-helix

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

Disease context

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

Also linked: Fanconi anemia complementation group D2 Fanconi anemia

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-asp381 (accessed [today's date]).

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