Is FANCD2 p.Ala329Pro (c.985G>C) pathogenic?

FANCD2 p.Ala329Pro (c.985G>C) is classified Uncertain significance in FANCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-02). AlphaMissense: likely benign (0.102); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FANCD2 p.Ala329Pro (c.985G>C)?

FANCD2 p.Ala329Pro (c.985G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FANCD2 p.Ala329Pro (c.985G>C) in the general population?

FANCD2 p.Ala329Pro (c.985G>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about FANCD2 p.Ala329Pro (c.985G>C)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

FANCD2 p.Ala329Pro

c.985G>C · rs765666007 · VCV1319366

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.01	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 0.44	GERP -1.9
Regional constraint	o/e 1.03	unconstrained · MANE · 15 kb · p 0.52 · regional, not allelic
Overall
CADD	15.42	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 0.000509% European (non-Finnish) · 6/1,179,640 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,461,416 alleles · very rare

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.Ala329Pro
Coding: c.985G>C
MANE Select: NM_001018115
dbSNP: rs765666007
Type: single nucleotide variant
Location: chr3:10043146 (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 329: the 'interaction with brca2' region

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.Ala329Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
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-ala329pro (accessed [today's date]).

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