Is CCER2 p.Glu64Asp (c.192G>C) pathogenic?

CCER2 p.Glu64Asp (c.192G>C) is classified Benign in CCER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: ambiguous (0.4953); Low-frequency (popmax 1.3%, eas).

How common is CCER2 p.Glu64Asp (c.192G>C) in the general population?

CCER2 p.Glu64Asp (c.192G>C) is low-frequency (popmax 1.3%, eas) (gnomAD).

What do computational predictors say about CCER2 p.Glu64Asp (c.192G>C)?

AlphaMissense predicts ambiguous (score 0.4953) — an in-silico prediction, not a clinical call.

CCER2 p.Glu64Asp

c.192G>C · rs375222589 · VCV2859091

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4953 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, eas)

Computational evidence

Protein change
AlphaMissense	0.4953	ambiguous · top 6% in CCER2
SaProt	LLR -8.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	GERP -0.008, phastCons 0.98
Regional constraint	o/e 1.02	unconstrained · MANE · 2,919 bp · p 0.73 · regional, not allelic
Overall
CADD	16.25	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 1.3% East Asian · 515/39,480 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 0.105% 1,491/1,417,834 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.3%	77
South Asian	0.461%	217
Remaining individualsnot grpmax-eligible	0.182%	548
Middle Eastern	0.129%	776
European (non-Finnish)	0.0524%	1,909
Admixed American	0.0145%	6,914
African / African-American	0.0115%	8,705
Finnishnot grpmax-eligible	0.00252%	39,614

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: CCER2
Protein: p.Glu64Asp
Coding: c.192G>C
MANE Select: NM_001243212
dbSNP: rs375222589
Type: single nucleotide variant
Location: chr19:38911082 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 64: a UniProt-annotated variant site (in)

Full CCER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCER2 p.Glu33Asp Benign ★★ ⚠ same type
CCER2 c.102+7A>T Uncertain significance ★ same type
CCER2 p.Ala121Gly Uncertain significance ★ ⚠ same type
CCER2 p.Ala21Ser Uncertain significance ★ ⚠ same type
CCER2 p.Arg123Leu Uncertain significance ★ ⚠ same type
CCER2 p.Arg143Lys Uncertain significance ★ ⚠ same type
CCER2 p.Arg195His Uncertain significance ★ ⚠ same type
CCER2 p.Glu202Lys Uncertain significance ★ ⚠ 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/ccer2-p-glu64asp (accessed [today's date]).

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