Is CCNC p.Thr252Ala (c.754A>G) pathogenic?

CCNC p.Thr252Ala (c.754A>G) is classified Uncertain significance in CCNC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-16). AlphaMissense: likely benign (0.0504); Very rare (popmax 0.00447%, eas).

How common is CCNC p.Thr252Ala (c.754A>G) in the general population?

CCNC p.Thr252Ala (c.754A>G) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about CCNC p.Thr252Ala (c.754A>G)?

AlphaMissense predicts likely benign (score 0.0504) — an in-silico prediction, not a clinical call.

CCNC p.Thr252Ala

c.754A>G · rs1202801256 · VCV2238024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0504 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0504	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.59, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 25 kb · p 2.1e-12 · regional, not allelic
Overall
CADD	16.35	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 0.00447% East Asian · 2/44,766 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.00048% 7/1,458,758 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,383
South Asian	0.0044%	22,750
European (non-Finnish)	8.49e-05%	1,177,388

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.Thr252Ala
Coding: c.754A>G
MANE Select: NM_005190
dbSNP: rs1202801256
Type: single nucleotide variant
Location: chr6:99545155 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 36 PDB
Residue 252: the 'disordered' region; 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-thr252ala (accessed [today's date]).

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