Is FANCI p.Ala1237Pro (c.3709G>C) pathogenic?

FANCI p.Ala1237Pro (c.3709G>C) is classified Uncertain significance in FANCI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1148); Ultra-rare (popmax 0.0274%, sas); Associated with Inborn genetic diseases.

What condition is associated with FANCI p.Ala1237Pro (c.3709G>C)?

FANCI p.Ala1237Pro (c.3709G>C) is associated with Inborn genetic diseases, Fanconi anemia complementation group I, Fanconi anemia (ClinVar).

How common is FANCI p.Ala1237Pro (c.3709G>C) in the general population?

FANCI p.Ala1237Pro (c.3709G>C) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about FANCI p.Ala1237Pro (c.3709G>C)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

FANCI p.Ala1237Pro

c.3709G>C · rs751025656 · VCV1675074

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -7.60	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 0.003	GERP -0.84
Regional constraint	o/e 1.12	unconstrained · MANE · 40 kb · p 0.00011 · regional, not allelic
Overall
CADD	6.347	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 0.0274% South Asian · 25/91,080 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00186% 30/1,613,900 alleles · ultra-rare exomes 29/1,461,822 · genomes 1/152,078 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00134%	74,876
European (non-Finnish)	8.47e-05%	1,179,979

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.Ala1237Pro
Coding: c.3709G>C
MANE Select: NM_001113378
dbSNP: rs751025656
Type: single nucleotide variant
Location: chr15:89312961 (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 1237: an α-helix

Full FANCI 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 I Fanconi anemia

Similar variants

FANCI p.Ala1237Gly Uncertain significance ★ ⚠ same residue
FANCI p.Ala1237Thr Uncertain significance ★ ⚠ same residue
POLG p.Pro1237Leu Uncertain significance ★★ ⚠ same residue
POLG p.Pro1237= Likely benign ★ same residue
POLG c.*100G>A Uncertain significance ★★★ same condition
POLG c.*122G>A Uncertain significance ★★★ same condition
FANCI c.1512+1G>A Likely pathogenic ★★ same condition
FANCI c.158-2A>G Pathogenic/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-ala1237pro (accessed [today's date]).

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