Is CEP57 p.Ala4Val (c.11C>T) pathogenic?

CEP57 p.Ala4Val (c.11C>T) is classified Uncertain significance in CEP57 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). AlphaMissense: ambiguous (0.5375); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Ala4Val (c.11C>T)?

CEP57 p.Ala4Val (c.11C>T) is associated with Inborn genetic diseases, mosaic variegated aneuploidy syndrome 2 (ClinVar).

How common is CEP57 p.Ala4Val (c.11C>T) in the general population?

CEP57 p.Ala4Val (c.11C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CEP57 p.Ala4Val (c.11C>T)?

AlphaMissense predicts ambiguous (score 0.5375) — an in-silico prediction, not a clinical call.

CEP57 p.Ala4Val

c.11C>T · VCV3831987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5375 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5375	ambiguous
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	25.2	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 0.00167% Admixed American · 1/60,016 alleles

Overall 0.000124% 2/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,016
South Asian	0.0011%	91,040

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.Ala4Val
Coding: c.11C>T
MANE Select: NM_014679
Type: single nucleotide variant
Location: chr11:95790709 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 4: the 'disordered' 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

Also linked: mosaic variegated aneuploidy syndrome 2

Similar variants

CEP57 p.Ala4Gly Uncertain significance ★★ ⚠ same residue
CEP57 p.Ala4Pro Uncertain significance ★ ⚠ same residue
CEP57 p.Ala4Ser Uncertain significance ★ ⚠ same residue
CEP57 p.Arg339Ter Pathogenic ★★ same condition
CEP57 c.202+6C>T Uncertain significance ★★ same condition
CEP57 p.Ala19Gly Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Thr Uncertain significance ★★ ⚠ same condition
CEP57 p.Ala278Val 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-ala4val (accessed [today's date]).

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