Is CC2D2A p.Arg982His (c.2945G>A) pathogenic?

CC2D2A p.Arg982His (c.2945G>A) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1167); Rare (popmax 0.174%, afr); Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Arg982His (c.2945G>A)?

CC2D2A p.Arg982His (c.2945G>A) is associated with Meckel syndrome, intellectual disability, Meckel syndrome, type 6 (ClinVar).

How common is CC2D2A p.Arg982His (c.2945G>A) in the general population?

CC2D2A p.Arg982His (c.2945G>A) is rare (popmax 0.174%, afr) (gnomAD).

What do computational predictors say about CC2D2A p.Arg982His (c.2945G>A)?

AlphaMissense predicts likely benign (score 0.1167) — an in-silico prediction, not a clinical call.

CC2D2A p.Arg982His

c.2945G>A · rs150093365 · VCV288560

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1167 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.174%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Meckel syndrome

Computational evidence

Protein change
AlphaMissense	0.1167	likely benign
REVEL	0.672	pathogenic-leaning
SaProt	LLR -7.11	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	29.6	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 0.174% African / African-American · 126/72,550 alleles

Filtering AF 0.149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.14%

Overall 0.0119% 181/1,517,768 alleles · rare exomes 95/1,365,692 · genomes 86/152,076 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.174%	576
Admixed American	0.0283%	3,535
East Asian	0.0231%	4,327
Remaining individualsnot grpmax-eligible	0.0152%	6,580
South Asian	0.00361%	27,726
European (non-Finnish)	0.00154%	64,949

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.Arg982His
Coding: c.2945G>A
MANE Select: NM_001378615
dbSNP: rs150093365
Type: single nucleotide variant
Location: chr4:15560553 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46

Full CC2D2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meckel syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability Meckel syndrome, type 6 Joubert syndrome 9 Joubert syndrome COACH syndrome 1

Similar variants

CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.1149+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.123+2T>G Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>C Likely pathogenic ★★ same condition
CC2D2A c.1466+1G>A Likely pathogenic ★★ same condition
CC2D2A c.1466+2T>C Likely pathogenic ★★ same condition
CC2D2A c.1608-2A>G Likely pathogenic ★★ 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-arg982his (accessed [today's date]).

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