Is FANCD2 p.Val97Ile (c.289G>A) pathogenic?

FANCD2 p.Val97Ile (c.289G>A) is classified Uncertain significance in FANCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-13). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0164%, eas); Associated with Fanconi anemia complementation group D2.

What condition is associated with FANCD2 p.Val97Ile (c.289G>A)?

FANCD2 p.Val97Ile (c.289G>A) is associated with Fanconi anemia complementation group D2, Fanconi anemia (ClinVar).

How common is FANCD2 p.Val97Ile (c.289G>A) in the general population?

FANCD2 p.Val97Ile (c.289G>A) is ultra-rare (popmax 0.0164%, eas) (gnomAD).

What do computational predictors say about FANCD2 p.Val97Ile (c.289G>A)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

FANCD2 p.Val97Ile

c.289G>A · rs1480379325 · VCV850071

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia complementation group D2

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.4	GERP 0.9, phastCons 0.59
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.52 · regional, not allelic
Overall
CADD	13.39	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% East Asian · 7/42,774 alleles

Filtering AF 0.00767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00535%

Overall 0.00109% 17/1,565,662 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0164%	6,111
Admixed American	0.0113%	8,840
South Asian	0.00116%	85,938
European (non-Finnish)	0.00026%	384,713

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.Val97Ile
Coding: c.289G>A
MANE Select: NM_001018115
dbSNP: rs1480379325
Type: single nucleotide variant
Location: chr3:10034710 (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 97: 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

Also linked: 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-val97ile (accessed [today's date]).

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