Is CERT1 p.Ser57Cys (c.170C>G) pathogenic?

CERT1 p.Ser57Cys (c.170C>G) is classified Uncertain significance in CERT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-04). AlphaMissense: ambiguous (0.4137); Absent from gnomAD v4.1; Associated with CERT1-related disorder.

What condition is associated with CERT1 p.Ser57Cys (c.170C>G)?

CERT1 p.Ser57Cys (c.170C>G) is associated with CERT1-related disorder (ClinVar).

How common is CERT1 p.Ser57Cys (c.170C>G) in the general population?

CERT1 p.Ser57Cys (c.170C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERT1 p.Ser57Cys (c.170C>G)?

AlphaMissense predicts ambiguous (score 0.4137) — an in-silico prediction, not a clinical call.

CERT1 p.Ser57Cys

c.170C>G · VCV3347487

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4137 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

CERT1-related disorder

Computational evidence

Protein change
AlphaMissense	0.4137	ambiguous
REVEL	0.494	indeterminate
SaProt	LLR -8.19	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 94 kb · p 1.1e-13 · regional, not allelic
Overall
CADD	30.0	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

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: CERT1
Protein: p.Ser57Cys
Coding: c.170C>G
MANE Select: NM_001379029
Type: single nucleotide variant
Location: chr5:75506043 (GRCh38)
Gene constraint: LOEUF 0.656 · pLI 0.10 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 77.75 · 27 PDB
Residue 57: the ph domain

Full CERT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CERT1-related disorder

Similar variants

CERT1 p.Ser57Tyr Likely pathogenic ★ same residue
CERT1 p.Ser132Thr Likely pathogenic ★ same condition
CERT1 c.1189-8T>C Benign same condition
CERT1 p.Asn221= Likely benign same condition
CERT1 p.Ile439= Likely benign same condition
CERT1 p.Leu347= Likely benign same condition
CERT1 p.Ser135Phe Likely pathogenic ★★ same type
CERT1 p.Thr166Ala Pathogenic/Likely pathogenic ★★ ⚠ 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/cert1-p-ser57cys (accessed [today's date]).

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