Is FANCD2 p.Pro852Ser (c.2554C>T) pathogenic?

FANCD2 p.Pro852Ser (c.2554C>T) is classified Uncertain significance in FANCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0861); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with FANCD2 p.Pro852Ser (c.2554C>T)?

FANCD2 p.Pro852Ser (c.2554C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FANCD2 p.Pro852Ser (c.2554C>T) in the general population?

FANCD2 p.Pro852Ser (c.2554C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about FANCD2 p.Pro852Ser (c.2554C>T)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

FANCD2 p.Pro852Ser

c.2554C>T · rs777727311 · VCV1337819

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -5.22	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	18.64	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 0.00401% African / African-American · 3/74,874 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000869% 14/1,611,834 alleles · very rare exomes 11/1,459,678 · genomes 3/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,958
European (non-Finnish)	0.000934%	107,102

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.Pro852Ser
Coding: c.2554C>T
MANE Select: NM_001018115
dbSNP: rs777727311
Type: single nucleotide variant
Location: chr3:10072930 (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

Similar variants

FANCD2 p.Pro852Arg Uncertain significance ★★ ⚠ same residue
FANCD2 p.Pro852Leu Uncertain significance ★★ ⚠ same residue
FANCD2 p.Pro852= Likely benign ★ same residue
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

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-pro852ser (accessed [today's date]).

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