Is CC2D2A p.Arg71His (c.212G>A) pathogenic?

CC2D2A p.Arg71His (c.212G>A) is classified Likely benign in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). AlphaMissense: likely benign (0.0624); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with CC2D2A p.Arg71His (c.212G>A)?

CC2D2A p.Arg71His (c.212G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D2A p.Arg71His (c.212G>A) in the general population?

CC2D2A p.Arg71His (c.212G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CC2D2A p.Arg71His (c.212G>A)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

CC2D2A p.Arg71His

c.212G>A · VCV3827993

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -7.15	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 -2.8	GERP -4.5
Regional constraint	o/e 0.96	unconstrained · MANE · 104 kb · p 0.09 · regional, not allelic
Overall
CADD	0.584	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000558% 9/1,613,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00446%	22,414
African / African-American	0.00267%	37,444
Admixed American	0.00167%	59,944
European (non-Finnish)	0.000254%	393,195

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.Arg71His
Coding: c.212G>A
MANE Select: NM_001378615
Type: single nucleotide variant
Location: chr4:15480792 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 71: 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.Arg71Cys Uncertain significance ★★ ⚠ same residue
CC2D2A p.Arg71= Likely benign ★ 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

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-arg71his (accessed [today's date]).

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