Is CEP57 p.Phe371Tyr (c.1112T>A) pathogenic?

CEP57 p.Phe371Tyr (c.1112T>A) is classified Uncertain significance in CEP57 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-29). AlphaMissense: likely benign (0.2757); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CEP57 p.Phe371Tyr (c.1112T>A)?

CEP57 p.Phe371Tyr (c.1112T>A) is associated with Inborn genetic diseases (ClinVar).

How common is CEP57 p.Phe371Tyr (c.1112T>A) in the general population?

CEP57 p.Phe371Tyr (c.1112T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CEP57 p.Phe371Tyr (c.1112T>A)?

AlphaMissense predicts likely benign (score 0.2757) — an in-silico prediction, not a clinical call.

CEP57 p.Phe371Tyr

c.1112T>A · VCV4000992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2757 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2757	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 41 kb · p 0.29 · regional, not allelic
Overall
CADD	26.2	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

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: CEP57
Protein: p.Phe371Tyr
Coding: c.1112T>A
MANE Select: NM_014679
Type: single nucleotide variant
Location: chr11:95828012 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.32 · 3 PDB
Residue 371: an α-helix; the 'mediates interaction with microtubules' 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.Phe371Leu 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-phe371tyr (accessed [today's date]).

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