Is CC2D1A p.Pro467Ala (c.1399C>G) pathogenic?

CC2D1A p.Pro467Ala (c.1399C>G) is classified Benign/Likely benign in CC2D1A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-26). AlphaMissense: likely benign (0.0471); Rare (popmax 0.203%, afr); Associated with intellectual disability, autosomal recessive 3.

What condition is associated with CC2D1A p.Pro467Ala (c.1399C>G)?

CC2D1A p.Pro467Ala (c.1399C>G) is associated with intellectual disability, autosomal recessive 3 (ClinVar).

How common is CC2D1A p.Pro467Ala (c.1399C>G) in the general population?

CC2D1A p.Pro467Ala (c.1399C>G) is rare (popmax 0.203%, afr) (gnomAD).

What do computational predictors say about CC2D1A p.Pro467Ala (c.1399C>G)?

AlphaMissense predicts likely benign (score 0.0471) — an in-silico prediction, not a clinical call.

CC2D1A p.Pro467Ala

c.1399C>G · rs199717745 · VCV714883

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0471 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.203%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 3

Computational evidence

Protein change
AlphaMissense	0.0471	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.39	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 -0.89	GERP -4.7
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	0.511	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 0.203% African / African-American · 152/74,804 alleles

Filtering AF 0.177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.0106% 170/1,610,346 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.203%	492
Remaining individualsnot grpmax-eligible	0.016%	6,231
Admixed American	0.0118%	8,503
European (non-Finnish)	8.49e-05%	1,178,144

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.Pro467Ala
Coding: c.1399C>G
MANE Select: NM_017721
dbSNP: rs199717745
Type: single nucleotide variant
Location: chr19:13920599 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 467: the 'disordered' region

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

Disease context

intellectual disability, autosomal recessive 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CC2D1A p.Pro467= Likely benign ★★ same residue
CC2D1A p.Pro467Leu Uncertain significance ★ ⚠ 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.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-pro467ala (accessed [today's date]).

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