Is CEP44 p.Ser46Pro (c.136T>C) pathogenic?

CEP44 p.Ser46Pro (c.136T>C) is classified Uncertain significance in CEP44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.9318); Very rare (popmax 0.00136%, nfe).

How common is CEP44 p.Ser46Pro (c.136T>C) in the general population?

CEP44 p.Ser46Pro (c.136T>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about CEP44 p.Ser46Pro (c.136T>C)?

AlphaMissense predicts likely pathogenic (score 0.9318) — an in-silico prediction, not a clinical call.

CEP44 p.Ser46Pro

c.136T>C · VCV4652499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9318	likely pathogenic · top 7% in CEP44
REVEL	0.179	moderately benign-leaning
SaProt	LLR -11.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.52, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 18 kb · p 0.48 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,336 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.000993% 16/1,611,478 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: CEP44
Protein: p.Ser46Pro
Coding: c.136T>C
MANE Select: NM_001040157
Type: single nucleotide variant
Location: chr4:174302085 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.41 · 1 PDB
Residue 46: the 'binds with microtubules and centrioles' region; an α-helix

Full CEP44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP44 p.Ala102Gly Uncertain significance ★ ⚠ same type
CEP44 p.Ala155Thr Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Ser Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Thr Uncertain significance ★ ⚠ same type
CEP44 p.Ala172Val Uncertain significance ★ ⚠ same type
CEP44 p.Ala349Gly Uncertain significance ★ ⚠ same type
CEP44 p.Arg11Gln Uncertain significance ★ ⚠ same type
CEP44 p.Arg176Cys 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/cep44-p-ser46pro (accessed [today's date]).

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