Is CFC1 p.Ile19Val (c.55A>G) pathogenic?

CFC1 p.Ile19Val (c.55A>G) is classified Uncertain significance in CFC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.1802); Very rare (popmax 0.000281%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CFC1 p.Ile19Val (c.55A>G)?

CFC1 p.Ile19Val (c.55A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CFC1 p.Ile19Val (c.55A>G) in the general population?

CFC1 p.Ile19Val (c.55A>G) is very rare (popmax 0.000281%, nfe) (gnomAD).

What do computational predictors say about CFC1 p.Ile19Val (c.55A>G)?

AlphaMissense predicts likely benign (score 0.1802) — an in-silico prediction, not a clinical call.

CFC1 p.Ile19Val

c.55A>G · VCV3832480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1802 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000281%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1802	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.42	phastCons 0.066
Regional constraint	o/e 0.12	constrained · MANE · 6,407 bp · p 3.7e-22 · regional, not allelic
Overall
CADD	10.48	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 0.000281% European (non-Finnish) · 2/712,564 alleles

Filtering AF 4.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.8e-05%

Overall 0.000221% 2/904,990 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: CFC1
Protein: p.Ile19Val
Coding: c.55A>G
MANE Select: NM_032545
Type: single nucleotide variant
Location: chr2:130598928 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.86 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.18

Full CFC1 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

CFC1 p.Gly33Ser Uncertain significance ★★ ⚠ same condition
CFC1 p.Gly59Arg Likely benign ★★ same condition
CFC1 p.Ala195Val Uncertain significance ★ ⚠ same condition
CFC1 p.Ala79Thr Uncertain significance ★ ⚠ same condition
CFC1 p.Arg28Gly Uncertain significance ★ ⚠ same condition
CFC1 p.Arg47Leu Uncertain significance ★ ⚠ same condition
CFC1 p.Glu72Lys Uncertain significance ★ ⚠ same condition
CFC1 p.His31Arg 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/cfc1-p-ile19val (accessed [today's date]).

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