Is CCER2 p.His71= (c.213C>T) pathogenic?

CCER2 p.His71= (c.213C>T) is classified Likely benign in CCER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). Ultra-rare (popmax 0.0718%, mid).

How common is CCER2 p.His71= (c.213C>T) in the general population?

CCER2 p.His71= (c.213C>T) is ultra-rare (popmax 0.0718%, mid) (gnomAD).

CCER2 p.His71=

c.213C>T · rs139537050 · VCV2715064

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0718%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -4.3
Overall
CADD	0.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0718% Middle Eastern · 4/5,570 alleles

Filtering AF 0.0245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0201% 293/1,456,340 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.41%	41
Middle Easterngrpmax	0.0718%	1,392
Remaining individualsnot grpmax-eligible	0.0266%	3,766
European (non-Finnish)	0.0213%	4,688
Admixed American	0.0213%	4,693
South Asian	0.00852%	11,740
East Asian	0.00248%	40,394

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His71=
Coding: c.213C>T
MANE Select: NM_001243212
dbSNP: rs139537050
Type: single nucleotide variant
Location: chr19:38911061 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.74

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-his71 (accessed [today's date]).

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