Is CCNC p.Phe195Leu (c.585C>A) pathogenic?

CCNC p.Phe195Leu (c.585C>A) is classified Uncertain significance in CCNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9939); Absent from gnomAD v4.1.

How common is CCNC p.Phe195Leu (c.585C>A) in the general population?

CCNC p.Phe195Leu (c.585C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCNC p.Phe195Leu (c.585C>A)?

AlphaMissense predicts likely pathogenic (score 0.9939) — an in-silico prediction, not a clinical call.

CCNC p.Phe195Leu

c.585C>A · VCV4650032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9939 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,158)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9939	likely pathogenic
REVEL	0.186	benign-leaning
SaProt	LLR -10.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 25 kb · p 2.1e-12 · regional, not allelic
Overall
CADD	23.1	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

No allele count reported in gnomAD v4.1 (AN 1,605,158). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CCNC
Protein: p.Phe195Leu
Coding: c.585C>A
MANE Select: NM_005190
Type: single nucleotide variant
Location: chr6:99549521 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 36 PDB
Residue 195: an α-helix

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-phe195leu (accessed [today's date]).

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