Is CCNP p.Arg275Lys (c.824G>A) pathogenic?

CCNP p.Arg275Lys (c.824G>A) is classified Uncertain significance in CCNP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.2272); Ultra-rare (popmax 0.0118%, amr).

How common is CCNP p.Arg275Lys (c.824G>A) in the general population?

CCNP p.Arg275Lys (c.824G>A) is ultra-rare (popmax 0.0118%, amr) (gnomAD).

What do computational predictors say about CCNP p.Arg275Lys (c.824G>A)?

AlphaMissense predicts likely benign (score 0.2272) — an in-silico prediction, not a clinical call.

CCNP p.Arg275Lys

c.824G>A · VCV3487490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2272 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2272	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -8.16	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 5.4	GERP 0.44, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,586 bp · p 0.45 · regional, not allelic
Overall
CADD	24.2	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 0.0118% Admixed American · 6/50,986 alleles

Filtering AF 0.00512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00347%

Overall 0.000773% 12/1,551,510 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0118%	8,498
Remaining individualsnot grpmax-eligible	0.00499%	20,028
European (non-Finnish)	0.000262%	382,327

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: CCNP
Protein: p.Arg275Lys
Coding: c.824G>A
MANE Select: NM_024877
Type: single nucleotide variant
Location: chr19:40223152 (GRCh38)
Gene constraint: LOEUF 1.397 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.87

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

Similar variants

CCNP p.Ala173Ser Uncertain significance ★ ⚠ same type
CCNP p.Ala186Val Uncertain significance ★ ⚠ same type
CCNP p.Ala243Val Uncertain significance ★ ⚠ same type
CCNP p.Ala265Thr Uncertain significance ★ ⚠ same type
CCNP p.Ala37Ser Uncertain significance ★ ⚠ same type
CCNP p.Ala68Glu Uncertain significance ★ ⚠ same type
CCNP p.Ala81Ser Uncertain significance ★ ⚠ same type
CCNP p.Arg101His 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/ccnp-p-arg275lys (accessed [today's date]).

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