Is CCNF p.Arg406Gln (c.1217G>A) pathogenic?

CCNF p.Arg406Gln (c.1217G>A) is classified Benign/Likely benign in CCNF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.137); Rare (popmax 0.874%, mid).

How common is CCNF p.Arg406Gln (c.1217G>A) in the general population?

CCNF p.Arg406Gln (c.1217G>A) is rare (popmax 0.874%, mid) (gnomAD).

What do computational predictors say about CCNF p.Arg406Gln (c.1217G>A)?

AlphaMissense predicts likely benign (score 0.137) — an in-silico prediction, not a clinical call.

CCNF p.Arg406Gln

c.1217G>A · rs146438723 · VCV735821

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.137 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.874%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.137	likely benign
REVEL	0.236	benign-leaning
SaProt	LLR -5.78	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	33.0	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 0.874% Middle Eastern · 53/6,062 alleles

Filtering AF 0.732% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.713%

Overall 0.197% 3,179/1,613,722 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.874%	114
South Asian	0.78%	128
Ashkenazi Jewishnot grpmax-eligible	0.345%	290
Remaining individualsnot grpmax-eligible	0.235%	425
European (non-Finnish)	0.17%	587
Admixed American	0.137%	732
Finnishnot grpmax-eligible	0.0891%	1,122
African / African-American	0.0227%	4,413
East Asian	0.00446%	22,439

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.Arg406Gln
Coding: c.1217G>A
MANE Select: NM_001761
dbSNP: rs146438723
Type: single nucleotide variant
Location: chr16:2448977 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB

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

Similar variants

CCNF p.Ser621Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
CCNF p.Arg140Gln Uncertain significance ★★ ⚠ 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
CCNF c.1095-28A>G Benign ★★ same type
CCNF c.1095-7G>A Benign ★★ 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-arg406gln (accessed [today's date]).

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