Is CCNF p.Arg691Gln (c.2072G>A) pathogenic?

CCNF p.Arg691Gln (c.2072G>A) is classified Likely benign in CCNF (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-31). AlphaMissense: likely benign (0.074); Rare (popmax 0.123%, eas).

How common is CCNF p.Arg691Gln (c.2072G>A) in the general population?

CCNF p.Arg691Gln (c.2072G>A) is rare (popmax 0.123%, eas) (gnomAD).

What do computational predictors say about CCNF p.Arg691Gln (c.2072G>A)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

CCNF p.Arg691Gln

c.2072G>A · rs148419125 · VCV722268

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.76	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 -0.033	GERP -3.4
Regional constraint	o/e 0.98	unconstrained · MANE · 8,082 bp · p 0.66 · regional, not allelic
Overall
CADD	0.906	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 0.123% East Asian · 55/44,860 alleles

Filtering AF 0.0967% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0874%

Overall 0.0447% 720/1,612,246 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.123%	816
Ashkenazi Jewishnot grpmax-eligible	0.109%	921
Admixed American	0.104%	966
Remaining individualsnot grpmax-eligible	0.0705%	1,418
European (non-Finnish)	0.043%	2,326
Middle Eastern	0.0165%	6,058
South Asian	0.011%	9,090
African / African-American	0.0107%	9,377
Finnishnot grpmax-eligible	0.00157%	63,678

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.Arg691Gln
Coding: c.2072G>A
MANE Select: NM_001761
dbSNP: rs148419125
Type: single nucleotide variant
Location: chr16:2456731 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 72.34 · 1 PDB
Residue 691: the 'pest' region; the 'disordered' region

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-arg691gln (accessed [today's date]).

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