Is FANCD2 p.Pro90Thr (c.268C>A) pathogenic?

FANCD2 p.Pro90Thr (c.268C>A) is classified Uncertain significance in FANCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: ambiguous (0.5059); Absent from gnomAD v4.1; Associated with Fanconi anemia complementation group D2.

What condition is associated with FANCD2 p.Pro90Thr (c.268C>A)?

FANCD2 p.Pro90Thr (c.268C>A) is associated with Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Pro90Thr (c.268C>A) in the general population?

FANCD2 p.Pro90Thr (c.268C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FANCD2 p.Pro90Thr (c.268C>A)?

AlphaMissense predicts ambiguous (score 0.5059) — an in-silico prediction, not a clinical call.

FANCD2 p.Pro90Thr

c.268C>A · rs2086683082 · VCV3241573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5059 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,526)

Conditions

Fanconi anemia complementation group D2

Computational evidence

Protein change
AlphaMissense	0.5059	ambiguous
REVEL	0.301	indeterminate
SaProt	LLR -14.27	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.52 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,526). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FANCD2
Protein: p.Pro90Thr
Coding: c.268C>A
MANE Select: NM_001018115
dbSNP: rs2086683082
Type: single nucleotide variant
Location: chr3:10034531 (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 90: the 'interaction with fance' region; 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.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-pro90thr (accessed [today's date]).

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