Is CCNC p.Tyr76Asp (c.226T>G) pathogenic?

CCNC p.Tyr76Asp (c.226T>G) is classified Uncertain significance in CCNC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-06). AlphaMissense: likely pathogenic (0.8841); Absent from gnomAD v4.1.

How common is CCNC p.Tyr76Asp (c.226T>G) in the general population?

CCNC p.Tyr76Asp (c.226T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNC p.Tyr76Asp (c.226T>G)?

AlphaMissense predicts likely pathogenic (score 0.8841) — an in-silico prediction, not a clinical call.

CCNC p.Tyr76Asp

c.226T>G · rs2538443201 · VCV3139891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8841	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -9.25	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.52, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 25 kb · p 2.1e-12 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCNC
Protein: p.Tyr76Asp
Coding: c.226T>G
MANE Select: NM_005190
dbSNP: rs2538443201
Type: single nucleotide variant
Location: chr6:99561435 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 36 PDB
Residue 76: the cyclin n-terminal domain

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

Similar variants

CCNC p.Arg25Cys Uncertain significance ★ ⚠ same type
CCNC p.Arg25His Uncertain significance ★ ⚠ same type
CCNC p.Asp223Gly Uncertain significance ★ ⚠ same type
CCNC p.Gln209His Uncertain significance ★ ⚠ same type
CCNC p.Glu36Ter Uncertain significance ★ same type
CCNC p.Ile15Ser Uncertain significance ★ ⚠ same type
CCNC p.Lys256Arg Uncertain significance ★ ⚠ same type
CCNC p.Lys256Gln 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/ccnc-p-tyr76asp (accessed [today's date]).

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