Is EEA1 p.Pro44Ser (c.130C>T) pathogenic?

EEA1 p.Pro44Ser (c.130C>T) is classified Uncertain significance in EEA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely pathogenic (0.9802); Absent from gnomAD v4.1.

How common is EEA1 p.Pro44Ser (c.130C>T) in the general population?

EEA1 p.Pro44Ser (c.130C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EEA1 p.Pro44Ser (c.130C>T)?

AlphaMissense predicts likely pathogenic (score 0.9802) — an in-silico prediction, not a clinical call.

EEA1 p.Pro44Ser

c.130C>T · VCV3274531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9802 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9802	likely pathogenic · top 3% in EEA1
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -10.04	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 152 kb · p 3.5e-05 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: EEA1
Protein: p.Pro44Ser
Coding: c.130C>T
MANE Select: NM_003566
Type: single nucleotide variant
Location: chr12:92864975 (GRCh38)
Gene constraint: LOEUF 0.663 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.53 · 4 PDB
Residue 44: a turn

Full EEA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEA1 p.Asn1072Lys Benign ★★ same type
EEA1 p.Tyr718= Benign ★★ same type
EEA1 c.3468+1G>A Uncertain significance ★ same type
EEA1 c.4015-1G>C Uncertain significance ★ same type
EEA1 p.Ala1092Val Uncertain significance ★ ⚠ same type
EEA1 p.Ala1184Val Uncertain significance ★ ⚠ same type
EEA1 p.Ala1245Val Uncertain significance ★ ⚠ same type
EEA1 p.Ala393Val 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/eea1-p-pro44ser (accessed [today's date]).

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