Is CC2D1A p.Ala481Val (c.1442C>T) pathogenic?

CC2D1A p.Ala481Val (c.1442C>T) is classified Uncertain significance in CC2D1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-04). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0172%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Ala481Val (c.1442C>T)?

CC2D1A p.Ala481Val (c.1442C>T) is associated with Inborn genetic diseases, intellectual disability, autosomal recessive 3 (ClinVar).

How common is CC2D1A p.Ala481Val (c.1442C>T) in the general population?

CC2D1A p.Ala481Val (c.1442C>T) is ultra-rare (popmax 0.0172%, nfe) (gnomAD).

What do computational predictors say about CC2D1A p.Ala481Val (c.1442C>T)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

CC2D1A p.Ala481Val

c.1442C>T · rs201665162 · VCV1031992

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.69	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	GERP 1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	19.87	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 0.0172% European (non-Finnish) · 203/1,178,194 alleles

Filtering AF 0.0152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0145%

Overall 0.0135% 217/1,610,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0172%	5,804
Remaining individualsnot grpmax-eligible	0.0112%	8,903
Finnishnot grpmax-eligible	0.00314%	31,849
African / African-American	0.00268%	37,367
East Asian	0.00224%	44,696
South Asian	0.00221%	45,294

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: CC2D1A
Protein: p.Ala481Val
Coding: c.1442C>T
MANE Select: NM_017721
dbSNP: rs201665162
Type: single nucleotide variant
Location: chr19:13920642 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 481: the 'disordered' region

Full CC2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability, autosomal recessive 3

Similar variants

CC2D1A p.Ala481= Likely benign ★★ same residue
CC2D1A c.2225+1G>A Likely pathogenic ★★ same condition
CC2D1A c.2454+1G>A Likely pathogenic ★★ same condition
CC2D1A c.2710+1G>A Likely pathogenic ★★ same condition
CC2D1A c.61-2A>G Likely pathogenic ★★ same condition
CC2D1A c.748+1G>T Pathogenic ★★ same condition
CC2D1A c.1941-6C>T Uncertain significance ★★ same condition
CC2D1A c.2073+5G>T Uncertain significance ★★ same condition

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/cc2d1a-p-ala481val (accessed [today's date]).

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