Is CERK p.Phe136Ser (c.407T>C) pathogenic?

CERK p.Phe136Ser (c.407T>C) is classified Uncertain significance in CERK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.9794); Absent from gnomAD v4.1.

How common is CERK p.Phe136Ser (c.407T>C) in the general population?

CERK p.Phe136Ser (c.407T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERK p.Phe136Ser (c.407T>C)?

AlphaMissense predicts likely pathogenic (score 0.9794) — an in-silico prediction, not a clinical call.

CERK p.Phe136Ser

c.407T>C · VCV4001262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9794	likely pathogenic · top 3% in CERK
REVEL	0.348	indeterminate
SaProt	LLR -14.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 51 kb · p 0.099 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: CERK
Protein: p.Phe136Ser
Coding: c.407T>C
MANE Select: NM_022766
Type: single nucleotide variant
Location: chr22:46712266 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.86
Residue 136: the dagkc domain

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

Similar variants

CERK p.His113= Benign ★★ same type
CERK p.Pro509= Benign ★★ same type
CERK p.Thr461Met Benign ★★ same type
CERK p.Ala215Thr Uncertain significance ★ ⚠ same type
CERK p.Ala215Val Uncertain significance ★ ⚠ same type
CERK p.Ala238Ser Uncertain significance ★ ⚠ same type
CERK p.Ala238Thr Uncertain significance ★ same type
CERK p.Ala254Thr 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/cerk-p-phe136ser (accessed [today's date]).

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