Is FANCD2 p.Ser996= (c.2988C>T) pathogenic?

FANCD2 p.Ser996= (c.2988C>T) is classified Likely benign in FANCD2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-06-02). Absent from gnomAD v4.1; Associated with FANCD2-related disorder.

What condition is associated with FANCD2 p.Ser996= (c.2988C>T)?

FANCD2 p.Ser996= (c.2988C>T) is associated with FANCD2-related disorder (ClinVar).

How common is FANCD2 p.Ser996= (c.2988C>T) in the general population?

FANCD2 p.Ser996= (c.2988C>T) is absent from gnomAD v4.1 (gnomAD).

FANCD2 p.Ser996=

c.2988C>T · rs2125059418 · VCV3036320

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

FANCD2-related disorder

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 0.62	GERP 0.65, phastCons 0.12
Overall
CADD	9.224	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FANCD2
Protein: p.Ser996=
Coding: c.2988C>T
MANE Select: NM_001018115
dbSNP: rs2125059418
Type: single nucleotide variant
Location: chr3:10081111 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.24 · 13 PDB

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

Disease context

FANCD2-related disorder

Similar variants

FANCD2 p.Ser996Gly Uncertain significance ★★ ⚠ same residue
FANCD2 p.Ser996Arg Uncertain significance ★ ⚠ same residue
FANCD2 c.377+1G>A Likely pathogenic ★★ same condition
FANCD2 p.Arg1236His Pathogenic/Likely pathogenic ★★ ⚠ same condition
FANCD2 p.Pro989Ala Uncertain significance ★★ ⚠ same condition
FANCD2 p.Glu1153Ter Likely pathogenic ★ same condition
FANCD2 p.Ser250Ter Likely pathogenic ★ same condition
FANCD2 c.2605+1G>A Conflicting classifications of pathogenicity ★ 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-ser996 (accessed [today's date]).

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