Is CR2 p.Phe767Ser (c.2300T>C) pathogenic?

CR2 p.Phe767Ser (c.2300T>C) is classified Uncertain significance in CR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely pathogenic (0.5662); Absent from gnomAD v4.1.

How common is CR2 p.Phe767Ser (c.2300T>C) in the general population?

CR2 p.Phe767Ser (c.2300T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CR2 p.Phe767Ser (c.2300T>C)?

AlphaMissense predicts likely pathogenic (score 0.5662) — an in-silico prediction, not a clinical call.

CR2 p.Phe767Ser

c.2300T>C · rs2527225588 · VCV3027154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5662 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5662	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.42, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.0053 · regional, not allelic
Overall
CADD	15.56	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F708S vs ClinVar F767S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CR2
Protein: p.Phe767Ser
Coding: c.2300T>C
MANE Select: NM_001006658
dbSNP: rs2527225588
Type: single nucleotide variant
Location: chr1:207474300 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.18 · 9 PDB
Residue 708 UniProt numbering: the sushi 11 domain

Full CR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CR2 p.Phe767Leu Uncertain significance ★ ⚠ same residue
CR2 c.1225+1G>C Pathogenic ★★ same type
CR2 c.3089-1G>A Likely pathogenic ★★ same type
CR2 p.Arg142Ter Pathogenic/Likely pathogenic ★★ same type
CR2 p.Arg368Ter Pathogenic/Likely pathogenic ★★ same type
CR2 p.Arg392Ter Pathogenic/Likely pathogenic ★★ same type
CR2 p.Arg840Ter Pathogenic/Likely pathogenic ★★ same type
CR2 p.Cys154Ter Pathogenic ★★ same type

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-phe767ser (accessed [today's date]).

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