Is CR2 p.Ala117= (c.351C>T) pathogenic?

CR2 p.Ala117= (c.351C>T) is classified Likely benign in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with CR2 p.Ala117= (c.351C>T)?

CR2 p.Ala117= (c.351C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CR2 p.Ala117= (c.351C>T) in the general population?

CR2 p.Ala117= (c.351C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

CR2 p.Ala117=

c.351C>T · VCV3496792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.61	GERP 0.66, phastCons 0.097
Overall
CADD	7.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,613,690 alleles · very rare exomes 4/1,461,420 · genomes 0/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,960
European (non-Finnish)	8.48e-05%	1,179,880

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: CR2
Protein: p.Ala117=
Coding: c.351C>T
MANE Select: NM_001006658
Type: single nucleotide variant
Location: chr1:207466818 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 117: the sushi 2 domain; a β-strand

Full CR2 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

CR2 p.Ala117Val Uncertain significance ★ ⚠ same residue
CR2 p.Ala174Pro Uncertain significance ★★ ⚠ same condition
CR2 p.Ala3Ser Uncertain significance ★★ ⚠ same condition
CR2 p.Arg1063Cys Uncertain significance ★★ ⚠ same condition
CR2 p.Arg358Lys Uncertain significance ★★ ⚠ same condition
CR2 p.Arg643Cys Uncertain significance ★★ ⚠ same condition
CR2 p.Arg716Gln Uncertain significance ★★ same condition
CR2 p.Arg840Gly 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/cr2-p-ala117 (accessed [today's date]).

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