Is CC2D1A p.Ile412Val (c.1234A>G) pathogenic?

CC2D1A p.Ile412Val (c.1234A>G) is classified Conflicting classifications of pathogenicity in CC2D1A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.2145); Rare (popmax 0.417%, amr); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Ile412Val (c.1234A>G)?

CC2D1A p.Ile412Val (c.1234A>G) is associated with Inborn genetic diseases, intellectual disability, autosomal recessive 3 (ClinVar).

How common is CC2D1A p.Ile412Val (c.1234A>G) in the general population?

CC2D1A p.Ile412Val (c.1234A>G) is rare (popmax 0.417%, amr) (gnomAD).

What do computational predictors say about CC2D1A p.Ile412Val (c.1234A>G)?

AlphaMissense predicts likely benign (score 0.2145) — an in-silico prediction, not a clinical call.

CC2D1A p.Ile412Val

c.1234A>G · rs191830054 · VCV210590

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.2145 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.417%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2145	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.51	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	21.4	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 0.417% Admixed American · 248/59,520 alleles

Filtering AF 0.374% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.358%

Overall 0.277% 4,443/1,603,876 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.438%	228
Admixed Americangrpmax	0.417%	240
European (non-Finnish)	0.317%	315
Remaining individualsnot grpmax-eligible	0.291%	344
Middle Eastern	0.253%	396
African / African-American	0.1%	996
Finnishnot grpmax-eligible	0.0829%	1,206
South Asian	0.0231%	4,321
East Asian	0.00224%	44,586

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile412Val
Coding: c.1234A>G
MANE Select: NM_017721
dbSNP: rs191830054
Type: single nucleotide variant
Location: chr19:13919829 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB

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.Ile412Met 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.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-ile412val (accessed [today's date]).

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