Is CCIN p.Val418Ala (c.1253T>C) pathogenic?

CCIN p.Val418Ala (c.1253T>C) is classified Uncertain significance in CCIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-15). AlphaMissense: likely benign (0.3266); Ultra-rare (popmax 0.016%, afr).

How common is CCIN p.Val418Ala (c.1253T>C) in the general population?

CCIN p.Val418Ala (c.1253T>C) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about CCIN p.Val418Ala (c.1253T>C)?

AlphaMissense predicts likely benign (score 0.3266) — an in-silico prediction, not a clinical call.

CCIN p.Val418Ala

c.1253T>C · VCV3264454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3266 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3266	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,763 bp · p 7.5e-07 · regional, not allelic
Overall
CADD	21.0	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 0.016% African / African-American · 12/74,950 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00721%

Overall 0.000743% 12/1,614,152 alleles · ultra-rare

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.Val418Ala
Coding: c.1253T>C
MANE Select: NM_005893
Type: single nucleotide variant
Location: chr9:36170755 (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.Val418Met Uncertain significance ★ ⚠ same residue
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

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-val418ala (accessed [today's date]).

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