Is CR2 p.Asp243Val (c.728A>T) pathogenic?

CR2 p.Asp243Val (c.728A>T) is classified Uncertain significance in CR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-07). AlphaMissense: likely benign (0.1857); Ultra-rare (popmax 0.0574%, afr); Associated with Inborn genetic diseases.

What condition is associated with CR2 p.Asp243Val (c.728A>T)?

CR2 p.Asp243Val (c.728A>T) is associated with Inborn genetic diseases, immunodeficiency, common variable, 7 (ClinVar).

How common is CR2 p.Asp243Val (c.728A>T) in the general population?

CR2 p.Asp243Val (c.728A>T) is ultra-rare (popmax 0.0574%, afr) (gnomAD).

What do computational predictors say about CR2 p.Asp243Val (c.728A>T)?

AlphaMissense predicts likely benign (score 0.1857) — an in-silico prediction, not a clinical call.

CR2 p.Asp243Val

c.728A>T · rs368883636 · VCV571680

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0574%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1857	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.0053 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0574% African / African-American · 43/74,866 alleles

Filtering AF 0.0437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.039%

Overall 0.00316% 51/1,613,478 alleles · ultra-rare exomes 27/1,461,338 · genomes 24/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0574%	1,741
Admixed American	0.0117%	8,567
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Asp243Val
Coding: c.728A>T
MANE Select: NM_001006658
dbSNP: rs368883636
Type: single nucleotide variant
Location: chr1:207468893 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 243: the sushi 4 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

Also linked: immunodeficiency, common variable, 7

Similar variants

CR2 p.Asp243= Likely benign ★ same residue
CR2 c.1225+1G>C Pathogenic ★★ same condition
CR2 c.3089-1G>A Likely pathogenic ★★ same condition
CR2 p.Arg142Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg368Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg392Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Arg840Ter Pathogenic/Likely pathogenic ★★ same condition
CR2 p.Cys154Ter 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/cr2-p-asp243val (accessed [today's date]).

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