Is CCER1 p.Pro43Ser (c.127C>T) pathogenic?

CCER1 p.Pro43Ser (c.127C>T) is classified Uncertain significance in CCER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely benign (0.1137); Absent from gnomAD v4.1.

How common is CCER1 p.Pro43Ser (c.127C>T) in the general population?

CCER1 p.Pro43Ser (c.127C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCER1 p.Pro43Ser (c.127C>T)?

AlphaMissense predicts likely benign (score 0.1137) — an in-silico prediction, not a clinical call.

CCER1 p.Pro43Ser

c.127C>T · VCV3264442

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1137 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1137	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.50	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 -0.29	GERP -3.5, phastCons 0.007
Regional constraint	o/e 1.09	unconstrained · MANE · 1,217 bp · p 0.034 · regional, not allelic
Overall
CADD	10.22	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

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: CCER1
Protein: p.Pro43Ser
Coding: c.127C>T
MANE Select: NM_152638
Type: single nucleotide variant
Location: chr12:90954616 (GRCh38)
Gene constraint: LOEUF 1.814 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 50.34
Residue 43: the 'disordered' region

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

Similar variants

CCER1 p.Pro43Leu Uncertain significance ★ ⚠ same residue
CCER1 p.Ala164Glu Uncertain significance ★ ⚠ same type
CCER1 p.Ala225Thr Uncertain significance ★ ⚠ same type
CCER1 p.Ala27Val 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

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-pro43ser (accessed [today's date]).

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