Is MCFD2 c.*445A>G pathogenic?

MCFD2 c.445A>G is classified Uncertain significance in MCFD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0932%, eas); Associated with factor 5 and Factor VIII, combined deficiency of, 2.

What condition is associated with MCFD2 c.*445A>G?

MCFD2 c.*445A>G is associated with factor 5 and Factor VIII, combined deficiency of, 2 (ClinVar).

How common is MCFD2 c.*445A>G in the general population?

MCFD2 c.*445A>G is ultra-rare (popmax 0.0932%, eas) (gnomAD).

How is Combined deficiency of factor V and factor VIII inherited?

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

MCFD2 c.*445A>G

rs1160902939 · VCV898098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0932%, eas)

Conditions

factor 5 and Factor VIII, combined deficiency of, 2

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 -0.37	GERP -0.28, phastCons 0.094
Overall
CADD	1.957	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0932% East Asian · 10/10,730 alleles

Filtering AF 0.0506% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00587% 16/272,802 alleles · ultra-rare exomes 7/120,506 · genomes 9/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0932%	1,073
Remaining individualsnot grpmax-eligible	0.0247%	4,052
African / African-American	0.00445%	22,450
European (non-Finnish)	0.00141%	70,801

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: MCFD2
Coding: c.*445A>G
MANE Select: NM_139279
dbSNP: rs1160902939
Type: single nucleotide variant
Location: chr2:46905018 (GRCh38)
Gene constraint: LOEUF 1.366 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.97 · 17 PDB

Full MCFD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor 5 and Factor VIII, combined deficiency of, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined deficiency of factor V and factor VIII (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

MCFD2 c.149+5G>A Likely pathogenic ★★ same condition
MCFD2 p.Ala139Val Uncertain significance ★★ same condition
MCFD2 p.Ile121Met Uncertain significance ★★ ⚠ same condition
MCFD2 c.310-11G>C Likely benign ★★ same condition
MCFD2 c.*1267G>T Benign ★★ same condition
MCFD2 c.*133A>T Benign ★★ same condition
MCFD2 c.*1677T>G Benign ★★ same condition
MCFD2 c.*1752T>C Benign ★★ 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/mcfd2-c-star-445a-g (accessed [today's date]).

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