Is FANCD2 p.Pro504Ala (c.1510C>G) pathogenic?

FANCD2 p.Pro504Ala (c.1510C>G) is classified Uncertain significance in FANCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: likely benign (0.0915); Very rare (popmax 8.55e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FANCD2 p.Pro504Ala (c.1510C>G)?

FANCD2 p.Pro504Ala (c.1510C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FANCD2 p.Pro504Ala (c.1510C>G) in the general population?

FANCD2 p.Pro504Ala (c.1510C>G) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about FANCD2 p.Pro504Ala (c.1510C>G)?

AlphaMissense predicts likely benign (score 0.0915) — an in-silico prediction, not a clinical call.

FANCD2 p.Pro504Ala

c.1510C>G · rs1484950525 · VCV2399772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0915	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.33	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 1.4	GERP 1.7, phastCons 0.97
Regional constraint	o/e 0.62	unconstrained · MANE · 5,919 bp · p 5.4e-07 · regional, not allelic
Overall
CADD	14.63	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 8.55e-05% European (non-Finnish) · 1/1,169,578 alleles

Overall 6.25e-05% 1/1,600,350 alleles · very rare exomes 1/1,448,686 · genomes 0/151,664 · 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.Pro504Ala
Coding: c.1510C>G
MANE Select: NM_001018115
dbSNP: rs1484950525
Type: single nucleotide variant
Location: chr3:10049470 (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 504: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FANCD2 p.Ala329Pro Uncertain significance ★★ ⚠ same condition
FANCD2 p.Arg315Gln Uncertain significance ★★ ⚠ same condition
FANCD2 p.Asn1213Lys Uncertain significance ★★ ⚠ same condition
FANCD2 p.Asn601Ser Uncertain significance ★★ ⚠ same condition
FANCD2 p.Cys342Tyr Uncertain significance ★★ ⚠ same condition
FANCD2 p.Cys657Ser Uncertain significance ★★ ⚠ same condition
FANCD2 p.Gln308Arg Uncertain significance ★★ ⚠ same condition
FANCD2 p.Gln706Glu Uncertain significance ★★ ⚠ 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-pro504ala (accessed [today's date]).

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