Is CCNP p.Cys211Tyr (c.632G>A) pathogenic?

CCNP p.Cys211Tyr (c.632G>A) is classified Uncertain significance in CCNP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.5737); Ultra-rare (popmax 0.0282%, nfe).

How common is CCNP p.Cys211Tyr (c.632G>A) in the general population?

CCNP p.Cys211Tyr (c.632G>A) is ultra-rare (popmax 0.0282%, nfe) (gnomAD).

What do computational predictors say about CCNP p.Cys211Tyr (c.632G>A)?

AlphaMissense predicts likely pathogenic (score 0.5737) — an in-silico prediction, not a clinical call.

CCNP p.Cys211Tyr

c.632G>A · rs761118637 · VCV2463395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5737 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5737	likely pathogenic
REVEL	0.22	benign-leaning
SaProt	LLR -6.43	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.2, 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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0282% European (non-Finnish) · 331/1,174,258 alleles

Filtering AF 0.0257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.0216% 345/1,600,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0282%	3,548
Remaining individualsnot grpmax-eligible	0.0129%	7,736
Admixed American	0.00514%	19,453
African / African-American	0.00402%	24,875

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.Cys211Tyr
Coding: c.632G>A
MANE Select: NM_024877
dbSNP: rs761118637
Type: single nucleotide variant
Location: chr19:40223428 (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-cys211tyr (accessed [today's date]).

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