Is CEP57 p.Asn65Ser (c.194A>G) pathogenic?

CEP57 p.Asn65Ser (c.194A>G) is classified Uncertain significance in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-05). AlphaMissense: likely benign (0.1462); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Asn65Ser (c.194A>G)?

CEP57 p.Asn65Ser (c.194A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP57 p.Asn65Ser (c.194A>G) in the general population?

CEP57 p.Asn65Ser (c.194A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CEP57 p.Asn65Ser (c.194A>G)?

AlphaMissense predicts likely benign (score 0.1462) — an in-silico prediction, not a clinical call.

CEP57 p.Asn65Ser

c.194A>G · VCV4868783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1462	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -5.34	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 9.2	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	21.6	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 0.00133% African / African-American · 1/75,044 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00041% 6/1,461,640 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,044
South Asian	0.0011%	91,074
European (non-Finnish)	0.000339%	294,975

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: CEP57
Protein: p.Asn65Ser
Coding: c.194A>G
MANE Select: NM_014679
Type: single nucleotide variant
Location: chr11:95799380 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 65: the 'centrosome localization domain (cld)' region

Full CEP57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP57 p.Asn65= Uncertain significance ★ same residue
CEP57 p.Ala19Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala412Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala4Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala4Val Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala68Val Uncertain significance ★★ ⚠ same condition
CEP57 p.Arg175Gln Uncertain significance ★★ ⚠ same condition

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/cep57-p-asn65ser (accessed [today's date]).

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