Is CCNI p.Lys28Thr (c.83A>C) pathogenic?

CCNI p.Lys28Thr (c.83A>C) is classified Uncertain significance in CCNI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: ambiguous (0.3572); Ultra-rare (popmax 0.0115%, nfe).

How common is CCNI p.Lys28Thr (c.83A>C) in the general population?

CCNI p.Lys28Thr (c.83A>C) is ultra-rare (popmax 0.0115%, nfe) (gnomAD).

What do computational predictors say about CCNI p.Lys28Thr (c.83A>C)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

CCNI p.Lys28Thr

c.83A>C · VCV3997647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0115%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.228	benign-leaning
SaProt	LLR -5.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.45, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 11 kb · p 4.1e-05 · regional, not allelic
Overall
CADD	25.8	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 0.0115% European (non-Finnish) · 136/1,179,982 alleles

Filtering AF 0.00994% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00931%

Overall 0.00867% 140/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0115%	8,676
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,024
African / African-American	0.00133%	74,940

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: CCNI
Protein: p.Lys28Thr
Coding: c.83A>C
MANE Select: NM_006835
Type: single nucleotide variant
Location: chr4:77066280 (GRCh38)
Gene constraint: LOEUF 0.574 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 72.93

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

Similar variants

CCNI p.Ala190Thr Uncertain significance ★ ⚠ same type
CCNI p.Arg240Gln Uncertain significance ★ ⚠ same type
CCNI p.Arg32Gln Uncertain significance ★ ⚠ same type
CCNI p.Arg32Trp Uncertain significance ★ ⚠ same type
CCNI p.Asn39His Uncertain significance ★ ⚠ same type
CCNI p.Asn60Ser Uncertain significance ★ ⚠ same type
CCNI p.Asn9Tyr Uncertain significance ★ ⚠ same type
CCNI p.Asp117Val 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/ccni-p-lys28thr (accessed [today's date]).

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