Is CCER1 p.Ala27Val (c.80C>T) pathogenic?

CCER1 p.Ala27Val (c.80C>T) is classified Uncertain significance in CCER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-17). AlphaMissense: likely benign (0.2685); Very rare (popmax 0.00112%, sas).

How common is CCER1 p.Ala27Val (c.80C>T) in the general population?

CCER1 p.Ala27Val (c.80C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

What do computational predictors say about CCER1 p.Ala27Val (c.80C>T)?

AlphaMissense predicts likely benign (score 0.2685) — an in-silico prediction, not a clinical call.

CCER1 p.Ala27Val

c.80C>T · VCV4649874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2685	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 1,217 bp · p 0.034 · regional, not allelic
Overall
CADD	23.5	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 0.00112% South Asian · 1/89,156 alleles

Overall 6.93e-05% 1/1,442,394 alleles · very rare

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: CCER1
Protein: p.Ala27Val
Coding: c.80C>T
MANE Select: NM_152638
Type: single nucleotide variant
Location: chr12:90954663 (GRCh38)
Gene constraint: LOEUF 1.814 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 50.34

Full CCER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCER1 p.Ala164Glu Uncertain significance ★ ⚠ same type
CCER1 p.Ala225Thr Uncertain significance ★ ⚠ same type
CCER1 p.Ala297Thr Uncertain significance ★ ⚠ same type
CCER1 p.Arg142Gly Uncertain significance ★ ⚠ same type
CCER1 p.Arg145His Uncertain significance ★ ⚠ same type
CCER1 p.Arg155Leu Uncertain significance ★ ⚠ same type
CCER1 p.Asn195Asp Uncertain significance ★ ⚠ same type
CCER1 p.Asn233Asp 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/ccer1-p-ala27val (accessed [today's date]).

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