Is CCNP p.Arg4Thr (c.11G>C) pathogenic?

CCNP p.Arg4Thr (c.11G>C) is classified Uncertain significance in CCNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.164); Very rare (popmax 0.00461%, eas).

How common is CCNP p.Arg4Thr (c.11G>C) in the general population?

CCNP p.Arg4Thr (c.11G>C) is very rare (popmax 0.00461%, eas) (gnomAD).

What do computational predictors say about CCNP p.Arg4Thr (c.11G>C)?

AlphaMissense predicts likely benign (score 0.164) — an in-silico prediction, not a clinical call.

CCNP p.Arg4Thr

c.11G>C · VCV4222194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.164 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00461%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.164	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	donor loss · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,586 bp · p 0.45 · regional, not allelic
Overall
CADD	23.4	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 0.00461% East Asian · 2/43,400 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000286%

Overall 0.00014% 2/1,428,146 alleles · very rare

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.Arg4Thr
Coding: c.11G>C
MANE Select: NM_024877
Type: single nucleotide variant
Location: chr19:40226631 (GRCh38)
Gene constraint: LOEUF 1.397 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.87
Residue 4: the 'disordered' region

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-arg4thr (accessed [today's date]).

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