Is CCNF p.Arg451His (c.1352G>A) pathogenic?

CCNF p.Arg451His (c.1352G>A) is classified Likely benign in CCNF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely benign (0.0643); Very rare (popmax 0.00769%, sas).

How common is CCNF p.Arg451His (c.1352G>A) in the general population?

CCNF p.Arg451His (c.1352G>A) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CCNF p.Arg451His (c.1352G>A)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

CCNF p.Arg451His

c.1352G>A · rs767126159 · VCV2511824

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.23	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 -1.1	GERP -3.2
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	0.467	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 0.00769% South Asian · 7/91,064 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00248% 40/1,610,078 alleles · very rare exomes 39/1,457,856 · genomes 1/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,009
European (non-Finnish)	0.00271%	36,873
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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.Arg451His
Coding: c.1352G>A
MANE Select: NM_001761
dbSNP: rs767126159
Type: single nucleotide variant
Location: chr16:2449415 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 451: an α-helix

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-arg451his (accessed [today's date]).

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