Is CCIN p.Leu284Phe (c.850C>T) pathogenic?

CCIN p.Leu284Phe (c.850C>T) is classified Uncertain significance in CCIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: ambiguous (0.5462); Very rare (popmax 0.00446%, eas).

How common is CCIN p.Leu284Phe (c.850C>T) in the general population?

CCIN p.Leu284Phe (c.850C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CCIN p.Leu284Phe (c.850C>T)?

AlphaMissense predicts ambiguous (score 0.5462) — an in-silico prediction, not a clinical call.

CCIN p.Leu284Phe

c.850C>T · rs762028043 · VCV3139682

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5462	ambiguous
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.03	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 2.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,763 bp · p 7.5e-07 · 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

Grpmax group 0.00446% East Asian · 2/44,868 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00041% 6/1,461,818 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,434
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: CCIN
Protein: p.Leu284Phe
Coding: c.850C>T
MANE Select: NM_005893
dbSNP: rs762028043
Type: single nucleotide variant
Location: chr9:36170352 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 90.53

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

Similar variants

CCIN p.Arg485Trp Benign/Likely benign ★★ ⚠ same type
CCIN p.Ala197Val Uncertain significance ★ ⚠ same type
CCIN p.Ala200Glu Uncertain significance ★ ⚠ same type
CCIN p.Ala200Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala299Val Uncertain significance ★ ⚠ same type
CCIN p.Ala417Thr Uncertain significance ★ ⚠ same type
CCIN p.Ala536Ser Uncertain significance ★ ⚠ same type
CCIN p.Arg106Leu 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/ccin-p-leu284phe (accessed [today's date]).

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