Is CFD c.55+1G>A pathogenic?

CFD c.55+1G>A is classified Likely pathogenic in CFD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-24). Very rare (popmax 7.06e-05%); Associated with CFD-related disorder.

What condition is associated with CFD c.55+1G>A?

CFD c.55+1G>A is associated with CFD-related disorder (ClinVar).

How common is CFD c.55+1G>A in the general population?

CFD c.55+1G>A is very rare (popmax 7.06e-05%) (gnomAD).

CFD c.55+1G>A

VCV4939523

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 7.06e-05%)

Conditions

CFD-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +1	canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone
SpliceAI	Δ0.96	donor loss · deltas
Pangolin	Δ0.22	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Non-coding constraint	Z -0.19	1 kb window · o/e 1.01 · regional · uncalibrated
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.06e-05%

Overall 7.06e-05% 1/1,416,538 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: CFD
Coding: c.55+1G>A
MANE Select: NM_001928
Type: single nucleotide variant
Location: chr19:859745 (GRCh38)
Gene constraint: LOEUF 1.948 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.19 · 40 PDB

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

Disease context

CFD-related disorder

Similar variants

ELANE p.Ser126Leu Pathogenic ★★ ⚠ same condition
CFD p.Gln167His Uncertain significance ★★ ⚠ same condition
CFD c.212+1G>A Likely pathogenic ★ same condition
CFD c.-8G>A Likely benign same condition
CFD p.Glu89fs Likely pathogenic ★ same condition
CFD p.Val97fs Likely pathogenic ★ same condition
CFD c.212+2T>G Likely pathogenic ★★ same type
CFD c.56-1G>C Likely pathogenic ★★ same type

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/cfd-c-55-plus-1g-a (accessed [today's date]).

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