Is CCNC p.Ile15Ser (c.44T>G) pathogenic?

CCNC p.Ile15Ser (c.44T>G) is classified Uncertain significance in CCNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely pathogenic (0.8777); Ultra-rare (popmax 0.0103%, amr).

How common is CCNC p.Ile15Ser (c.44T>G) in the general population?

CCNC p.Ile15Ser (c.44T>G) is ultra-rare (popmax 0.0103%, amr) (gnomAD).

What do computational predictors say about CCNC p.Ile15Ser (c.44T>G)?

AlphaMissense predicts likely pathogenic (score 0.8777) — an in-silico prediction, not a clinical call.

CCNC p.Ile15Ser

c.44T>G · VCV4650031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8777 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8777	likely pathogenic
REVEL	0.375	indeterminate
SaProt	LLR -9.53	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 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 25 kb · p 2.1e-12 · regional, not allelic
Overall
CADD	27.6	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 0.0103% Admixed American · 6/58,374 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.0025% 40/1,598,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0103%	9,729
Finnishnot grpmax-eligible	0.00807%	12,395
Remaining individualsnot grpmax-eligible	0.00322%	31,013
European (non-Finnish)	0.0023%	43,390

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: CCNC
Protein: p.Ile15Ser
Coding: c.44T>G
MANE Select: NM_005190
Type: single nucleotide variant
Location: chr6:99562937 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 36 PDB

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.Lys256Arg Uncertain significance ★ ⚠ same type
CCNC p.Lys256Gln Uncertain significance ★ ⚠ same type
CCNC p.Lys56Asn 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-ile15ser (accessed [today's date]).

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