Is CCER1 p.Ser34Phe (c.101C>T) pathogenic?

CCER1 p.Ser34Phe (c.101C>T) is classified Uncertain significance in CCER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely benign (0.2913); Very rare (popmax 8.49e-05%, nfe).

How common is CCER1 p.Ser34Phe (c.101C>T) in the general population?

CCER1 p.Ser34Phe (c.101C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about CCER1 p.Ser34Phe (c.101C>T)?

AlphaMissense predicts likely benign (score 0.2913) — an in-silico prediction, not a clinical call.

CCER1 p.Ser34Phe

c.101C>T · VCV4649879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2913 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2913	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.26	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 1.5	GERP 0.14, phastCons 0.75
Regional constraint	o/e 1.09	unconstrained · MANE · 1,217 bp · p 0.034 · regional, not allelic
Overall
CADD	17.42	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 8.49e-05% European (non-Finnish) · 1/1,178,486 alleles

Overall 6.21e-05% 1/1,609,180 alleles · very rare exomes 1/1,456,948 · genomes 0/152,232 · joint denominator

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.Ser34Phe
Coding: c.101C>T
MANE Select: NM_152638
Type: single nucleotide variant
Location: chr12:90954642 (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.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
CCER1 p.Asn195Asp 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-ser34phe (accessed [today's date]).

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