Is CERS6 p.Pro355Ala (c.1063C>G) pathogenic?

CERS6 p.Pro355Ala (c.1063C>G) is classified Uncertain significance in CERS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0534); Absent from gnomAD v4.1.

How common is CERS6 p.Pro355Ala (c.1063C>G) in the general population?

CERS6 p.Pro355Ala (c.1063C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CERS6 p.Pro355Ala (c.1063C>G)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

CERS6 p.Pro355Ala

c.1063C>G · VCV4001309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0534	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.73	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 0.82	GERP 0.032, phastCons 0.95
Regional constraint	o/e 0.89	unconstrained · MANE · 313 kb · p 0.015 · regional, not allelic
Overall
CADD	14.45	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: CERS6
Protein: p.Pro355Ala
Coding: c.1063C>G
MANE Select: NM_203463
Type: single nucleotide variant
Location: chr2:168769570 (GRCh38)
Gene constraint: LOEUF 0.593 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 87.97 · 3 PDB
Residue 355: the 'disordered' region

Full CERS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS6 p.Ala30Ser Uncertain significance ★ ⚠ same type
CERS6 p.Ala326Val Uncertain significance ★ ⚠ same type
CERS6 p.Ala362Val Uncertain significance ★ ⚠ same type
CERS6 p.Ala6Val Uncertain significance ★ ⚠ same type
CERS6 p.Arg121Cys Uncertain significance ★ ⚠ same type
CERS6 p.Asn10Lys Uncertain significance ★ ⚠ same type
CERS6 p.Asn122Ser Uncertain significance ★ ⚠ same type
CERS6 p.Asn168Lys 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/cers6-p-pro355ala (accessed [today's date]).

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