Is CCER2 p.Arg195His (c.584G>A) pathogenic?

CCER2 p.Arg195His (c.584G>A) is classified Uncertain significance in CCER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely benign (0.0683); Ultra-rare (popmax 0.0195%, nfe).

How common is CCER2 p.Arg195His (c.584G>A) in the general population?

CCER2 p.Arg195His (c.584G>A) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

What do computational predictors say about CCER2 p.Arg195His (c.584G>A)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

CCER2 p.Arg195His

c.584G>A · rs144166216 · VCV2712177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4
Regional constraint	o/e 1.02	unconstrained · MANE · 2,919 bp · p 0.73 · regional, not allelic
Overall
CADD	0.002	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 0.0195% European (non-Finnish) · 223/1,145,468 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0159% 244/1,533,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,137
Middle Eastern	0.0167%	5,972
Admixed American	0.0158%	6,344
Remaining individualsnot grpmax-eligible	0.0134%	7,485
African / African-American	0.00547%	18,284

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.Arg195His
Coding: c.584G>A
MANE Select: NM_001243212
dbSNP: rs144166216
Type: single nucleotide variant
Location: chr19:38910690 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.74
Residue 195: a UniProt-annotated variant site (in); the 'disordered' region

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.Glu202Lys Uncertain significance ★ ⚠ same type
CCER2 p.Glu250Gln 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-arg195his (accessed [today's date]).

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