Is AEBP1 p.Phe699Ser (c.2096T>C) pathogenic?

AEBP1 p.Phe699Ser (c.2096T>C) is classified Uncertain significance in AEBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.2717); Absent from gnomAD v4.1.

How common is AEBP1 p.Phe699Ser (c.2096T>C) in the general population?

AEBP1 p.Phe699Ser (c.2096T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AEBP1 p.Phe699Ser (c.2096T>C)?

AlphaMissense predicts likely benign (score 0.2717) — an in-silico prediction, not a clinical call.

AEBP1 p.Phe699Ser

c.2096T>C · rs2484357141 · VCV2965848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2717 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2717	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 0.89, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,592 bp · p 0.004 · regional, not allelic
Overall
CADD	21.7	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: AEBP1
Protein: p.Phe699Ser
Coding: c.2096T>C
MANE Select: NM_001129
dbSNP: rs2484357141
Type: single nucleotide variant
Location: chr7:44112200 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 699: a UniProt-annotated variant site (in edscll2); the peptidase m14 domain; the 'interaction with pten' region

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

Similar variants

AEBP1 p.Phe699= Likely benign ★ same residue
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

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-phe699ser (accessed [today's date]).

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