Is CR2 p.Ser614Pro (c.1840T>C) pathogenic?

CR2 p.Ser614Pro (c.1840T>C) is classified Uncertain significance in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.1773); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CR2 p.Ser614Pro (c.1840T>C)?

CR2 p.Ser614Pro (c.1840T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CR2 p.Ser614Pro (c.1840T>C) in the general population?

CR2 p.Ser614Pro (c.1840T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CR2 p.Ser614Pro (c.1840T>C)?

AlphaMissense predicts likely benign (score 0.1773) — an in-silico prediction, not a clinical call.

CR2 p.Ser614Pro

c.1840T>C · rs2527222502 · VCV2313272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1773	likely benign
REVEL	0.459	indeterminate
SaProt	LLR -12.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP 0.59
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.0053 · regional, not allelic
Overall
CADD	15.82	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 8.48e-05% European (non-Finnish) · 1/1,179,930 alleles

Overall 6.2e-05% 1/1,614,016 alleles · very rare exomes 1/1,461,706 · genomes 0/152,310 · joint denominator

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.Ser614Pro
Coding: c.1840T>C
MANE Select: NM_001006658
dbSNP: rs2527222502
Type: single nucleotide variant
Location: chr1:207473041 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 614: the sushi 10 domain

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.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
CR2 p.Arg987Lys 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-ser614pro (accessed [today's date]).

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