Is CCNF p.Glu575Asp (c.1725G>C) pathogenic?

CCNF p.Glu575Asp (c.1725G>C) is classified Likely benign in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-09-21). AlphaMissense: likely benign (0.1538); Very rare (popmax 0.00912%, eas); Associated with amyotrophic lateral sclerosis.

What condition is associated with CCNF p.Glu575Asp (c.1725G>C)?

CCNF p.Glu575Asp (c.1725G>C) is associated with amyotrophic lateral sclerosis (ClinVar).

How common is CCNF p.Glu575Asp (c.1725G>C) in the general population?

CCNF p.Glu575Asp (c.1725G>C) is very rare (popmax 0.00912%, eas) (gnomAD).

How is Amyotrophic lateral sclerosis inherited?

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

What do computational predictors say about CCNF p.Glu575Asp (c.1725G>C)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

CCNF p.Glu575Asp

c.1725G>C · VCV4820028

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00912%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	14.58	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00912% East Asian · 4/43,838 alleles

Filtering AF 0.00303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.000379% 6/1,582,034 alleles · very rare exomes 6/1,429,700 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00912%	10,960
European (non-Finnish)	0.000173%	577,561

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: CCNF
Protein: p.Glu575Asp
Coding: c.1725G>C
MANE Select: NM_001761
Type: single nucleotide variant
Location: chr16:2455404 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 575: the 'disordered' region

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

Disease context

amyotrophic lateral sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Amyotrophic lateral sclerosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CCNF p.Arg140Gln Uncertain significance ★★ ⚠ same condition
CCNF p.Val640Met Uncertain significance ★ ⚠ same condition
CCNF p.Leu209Val Likely benign ★ ⚠ same condition
CCNF p.Ser621Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
CCNF p.Arg24Lys Uncertain significance ★★ ⚠ same type
CCNF p.Arg572Gln Uncertain significance ★★ ⚠ same type
CCNF p.Gly254Ala Uncertain significance ★★ ⚠ same type
CCNF p.Gly719Val Uncertain significance ★★ ⚠ 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/ccnf-p-glu575asp (accessed [today's date]).

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