Is CC2D2A p.Ala628Ser (c.1882G>T) pathogenic?

CC2D2A p.Ala628Ser (c.1882G>T) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.00169%, amr); Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Ala628Ser (c.1882G>T)?

CC2D2A p.Ala628Ser (c.1882G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D2A p.Ala628Ser (c.1882G>T) in the general population?

CC2D2A p.Ala628Ser (c.1882G>T) is very rare (popmax 0.00169%, amr) (gnomAD).

What do computational predictors say about CC2D2A p.Ala628Ser (c.1882G>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

CC2D2A p.Ala628Ser

c.1882G>T · VCV4606573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00169%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.42	donor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.4	GERP 0.49, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	16.42	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 0.00169% Admixed American · 1/59,326 alleles

Overall 0.000137% 2/1,456,782 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00169%	59,326
European (non-Finnish)	8.49e-05%	1,177,866

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: CC2D2A
Protein: p.Ala628Ser
Coding: c.1882G>T
MANE Select: NM_001378615
Type: single nucleotide variant
Location: chr4:15538016 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 628: the 'disordered' region

Full CC2D2A 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

Similar variants

CC2D2A p.Ala628Thr Uncertain significance ★ ⚠ same residue
CC2D2A p.Val1045Ala Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Ala323Thr Uncertain significance ★★ ⚠ same condition
CC2D2A p.Ala669Glu Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1028Gln Uncertain significance ★★ same condition
CC2D2A p.Arg1028Trp Uncertain significance ★★ same condition
CC2D2A p.Arg1168His Uncertain significance ★★ ⚠ same condition
CC2D2A p.Arg1177His 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/cc2d2a-p-ala628ser (accessed [today's date]).

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