Is AEBP1 p.Pro1007Ala (c.3019C>G) pathogenic?

AEBP1 p.Pro1007Ala (c.3019C>G) is classified Uncertain significance in AEBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-15). AlphaMissense: likely benign (0.1122); Very rare (popmax 0.00333%, amr).

How common is AEBP1 p.Pro1007Ala (c.3019C>G) in the general population?

AEBP1 p.Pro1007Ala (c.3019C>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AEBP1 p.Pro1007Ala (c.3019C>G)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

AEBP1 p.Pro1007Ala

c.3019C>G · rs1369645983 · VCV1931428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,592 bp · p 0.004 · regional, not allelic
Overall
CADD	23.3	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 0.00333% Admixed American · 2/60,016 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,062 alleles · very rare exomes 2/1,461,784 · genomes 0/152,278 · joint denominator

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.Pro1007Ala
Coding: c.3019C>G
MANE Select: NM_001129
dbSNP: rs1369645983
Type: single nucleotide variant
Location: chr7:44113803 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.99
Residue 1007: a UniProt-annotated variant site (in edscll2); the 'required for transcriptional repression' region; the 'interaction with mapk1 and mapk3' region

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

Similar variants

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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-pro1007ala (accessed [today's date]).

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