Is AEBP1 p.Pro296Ser (c.886C>T) pathogenic?

AEBP1 p.Pro296Ser (c.886C>T) is classified Uncertain significance in AEBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-08). AlphaMissense: likely benign (0.1004); Ultra-rare (popmax 0.0147%, sas).

How common is AEBP1 p.Pro296Ser (c.886C>T) in the general population?

AEBP1 p.Pro296Ser (c.886C>T) is ultra-rare (popmax 0.0147%, sas) (gnomAD).

What do computational predictors say about AEBP1 p.Pro296Ser (c.886C>T)?

AlphaMissense predicts likely benign (score 0.1004) — an in-silico prediction, not a clinical call.

AEBP1 p.Pro296Ser

c.886C>T · rs753288702 · VCV2102662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1004	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -8.45	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 4.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,592 bp · p 0.004 · regional, not allelic
Overall
CADD	20.6	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

Grpmax group 0.0147% South Asian · 13/88,190 alleles

Filtering AF 0.0087% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00691%

Overall 0.00125% 18/1,443,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0147%	6,784
Remaining individualsnot grpmax-eligible	0.00162%	61,660
European (non-Finnish)	0.000341%	293,076

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: AEBP1
Protein: p.Pro296Ser
Coding: c.886C>T
MANE Select: NM_001129
dbSNP: rs753288702
Type: single nucleotide variant
Location: chr7:44108030 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 296: the 'disordered' region

Full AEBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AEBP1 c.1018+1G>A Likely pathogenic ★★ same type
AEBP1 c.1630+1G>A Pathogenic ★★ same type
AEBP1 c.1630+2T>A Pathogenic ★★ same type
AEBP1 p.Arg595Ter Pathogenic ★★ same type
AEBP1 p.Cys581Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Cys868Ter Likely pathogenic ★★ same type
AEBP1 p.Gln781Ter Pathogenic/Likely pathogenic ★★ same type
AEBP1 p.Tyr428Ter 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/aebp1-p-pro296ser (accessed [today's date]).

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