Is CEP55 p.Ala244Pro (c.730G>C) pathogenic?

CEP55 p.Ala244Pro (c.730G>C) is classified Benign in CEP55 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.7193); Common (popmax 18.3%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CEP55 p.Ala244Pro (c.730G>C)?

AlphaMissense predicts likely pathogenic (score 0.7193) — an in-silico prediction, not a clinical call.

CEP55 p.Ala244Pro

Q: How common is CEP55 p.Ala244Pro (c.730G>C) in the general population?

CEP55 p.Ala244Pro (c.730G>C) is common (popmax 18.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.730G>C · rs41308663 · VCV1561126

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7193 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.3%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7193	likely pathogenic · top 6% in CEP55
REVEL	0.131	moderately benign-leaning
SaProt	LLR -12.24	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 4.5	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0058 · regional, not allelic
Overall
CADD	21.3	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 18.3% East Asian · 8,168/44,588 alleles

Filtering AF 18% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.9%

Overall 4.08% 65,454/1,603,104 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	18.3%	5
Admixed American	13.7%	7
Middle Eastern	7.71%	13
African / African-American	6.3%	16
Remaining individualsnot grpmax-eligible	5.33%	19
South Asian	5.3%	19
Amishnot grpmax-eligible	4.28%	23
Ashkenazi Jewishnot grpmax-eligible	4.21%	24
Finnishnot grpmax-eligible	3.49%	29
European (non-Finnish)	2.77%	36

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: CEP55
Protein: p.Ala244Pro
Coding: c.730G>C
MANE Select: NM_018131
dbSNP: rs41308663
Type: single nucleotide variant
Location: chr10:93516985 (GRCh38)
Gene constraint: LOEUF 1.138 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 4 PDB
Residue 244: a UniProt-annotated variant site (in march)

Full CEP55 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP55 p.Arg64Ter Pathogenic/Likely pathogenic ★★ same type
CEP55 p.Arg86Ter Pathogenic ★★ same type
CEP55 p.Ser425Ter Pathogenic ★★ same type
CEP55 p.Arg385Gln Uncertain significance ★★ ⚠ same type
CEP55 p.His293Arg Uncertain significance ★★ ⚠ same type
CEP55 p.Pro426Arg Uncertain significance ★★ ⚠ same type
CEP55 p.Ser2Phe Uncertain significance ★★ ⚠ same type
CEP55 p.Val127Ile 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/cep55-p-ala244pro (accessed [today's date]).

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