Is FANCD2 p.Pro852Arg (c.2555C>G) pathogenic?

FANCD2 p.Pro852Arg (c.2555C>G) is classified Uncertain significance in FANCD2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.1215); Ultra-rare (popmax 0.0427%, afr); Associated with Inborn genetic diseases.

What condition is associated with FANCD2 p.Pro852Arg (c.2555C>G)?

FANCD2 p.Pro852Arg (c.2555C>G) is associated with Inborn genetic diseases, Fanconi anemia complementation group D2, Fanconi anemia (ClinVar).

How common is FANCD2 p.Pro852Arg (c.2555C>G) in the general population?

FANCD2 p.Pro852Arg (c.2555C>G) is ultra-rare (popmax 0.0427%, afr) (gnomAD).

What do computational predictors say about FANCD2 p.Pro852Arg (c.2555C>G)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

FANCD2 p.Pro852Arg

c.2555C>G · rs375827113 · VCV241736

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -6.87	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 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 36 kb · p 0.0049 · regional, not allelic
Overall
CADD	23.5	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 0.0427% African / African-American · 32/74,862 alleles

Filtering AF 0.031% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0271%

Overall 0.00217% 35/1,611,744 alleles · ultra-rare exomes 9/1,459,622 · genomes 26/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0427%	2,339
Remaining individualsnot grpmax-eligible	0.00481%	20,799

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.Pro852Arg
Coding: c.2555C>G
MANE Select: NM_001018115
dbSNP: rs375827113
Type: single nucleotide variant
Location: chr3:10072931 (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

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

Also linked: Fanconi anemia complementation group D2 Fanconi anemia

Similar variants

FANCD2 p.Pro852Leu Uncertain significance ★★ ⚠ same residue
FANCD2 p.Pro852Ser Uncertain significance ★★ ⚠ same residue
FANCD2 p.Pro852= Likely benign ★ same residue
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

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-pro852arg (accessed [today's date]).

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