Is FANCI p.Pro103= (c.309A>G) pathogenic?

FANCI p.Pro103= (c.309A>G) is classified Likely benign in FANCI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). Very rare (popmax 0.000339%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCI p.Pro103= (c.309A>G)?

FANCI p.Pro103= (c.309A>G) is associated with Fanconi anemia (ClinVar).

How common is FANCI p.Pro103= (c.309A>G) in the general population?

FANCI p.Pro103= (c.309A>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FANCI p.Pro103=

c.309A>G · rs2505904815 · VCV2968954

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.2
Overall
CADD	2.131	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,022 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,850 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: FANCI
Protein: p.Pro103=
Coding: c.309A>G
MANE Select: NM_001113378
dbSNP: rs2505904815
Type: single nucleotide variant
Location: chr15:89261605 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.61 · 8 PDB
Residue 103: an α-helix

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

Disease context

Fanconi anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCI c.1512+1G>A Likely pathogenic ★★ same condition
FANCI c.158-2A>G Pathogenic/Likely pathogenic ★★ same condition
FANCI c.1584-1G>C Likely pathogenic ★★ same condition
FANCI c.1698+1G>A Likely pathogenic ★★ same condition
FANCI c.1891-2A>G Likely pathogenic ★★ same condition
FANCI c.2291+2T>A Likely pathogenic ★★ same condition
FANCI c.2292-1G>T Likely pathogenic ★★ same condition
FANCI c.2456+1G>A 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/fanci-p-pro103 (accessed [today's date]).

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