Is AEN p.Pro63Ser (c.187C>T) pathogenic?

AEN p.Pro63Ser (c.187C>T) is classified Uncertain significance in AEN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely benign (0.0688); Absent from gnomAD v4.1.

How common is AEN p.Pro63Ser (c.187C>T) in the general population?

AEN p.Pro63Ser (c.187C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AEN p.Pro63Ser (c.187C>T)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

AEN p.Pro63Ser

c.187C>T · VCV3274173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -6.21	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 1	GERP 1.9, phastCons 0.016
Regional constraint	o/e 1.06	unconstrained · MANE · 4,081 bp · p 0.21 · regional, not allelic
Overall
CADD	14.83	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: AEN
Protein: p.Pro63Ser
Coding: c.187C>T
MANE Select: NM_022767
Type: single nucleotide variant
Location: chr15:88626396 (GRCh38)
Gene constraint: LOEUF 1.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19

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

Similar variants

AEN p.Ala10Ser Uncertain significance ★ ⚠ same type
AEN p.Ala112Ser Uncertain significance ★ ⚠ same type
AEN p.Ala194Thr Uncertain significance ★ ⚠ same type
AEN p.Ala201Val Uncertain significance ★ ⚠ same type
AEN p.Ala45Ser Uncertain significance ★ ⚠ same type
AEN p.Arg125Trp Uncertain significance ★ ⚠ same type
AEN p.Arg131Cys Uncertain significance ★ ⚠ same type
AEN p.Arg131His 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/aen-p-pro63ser (accessed [today's date]).

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