Is EEA1 p.Gln613Arg (c.1838A>G) pathogenic?

EEA1 p.Gln613Arg (c.1838A>G) is classified Uncertain significance in EEA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1083); Very rare (popmax 0.0011%, sas).

How common is EEA1 p.Gln613Arg (c.1838A>G) in the general population?

EEA1 p.Gln613Arg (c.1838A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EEA1 p.Gln613Arg (c.1838A>G)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

EEA1 p.Gln613Arg

c.1838A>G · rs2500092288 · VCV2485008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 152 kb · p 3.5e-05 · regional, not allelic
Overall
CADD	24.0	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 0.0011% South Asian · 1/91,088 alleles

Overall 6.2e-05% 1/1,614,052 alleles · very rare exomes 1/1,461,726 · genomes 0/152,326 · 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: EEA1
Protein: p.Gln613Arg
Coding: c.1838A>G
MANE Select: NM_003566
dbSNP: rs2500092288
Type: single nucleotide variant
Location: chr12:92816291 (GRCh38)
Gene constraint: LOEUF 0.663 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.53 · 4 PDB

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-gln613arg (accessed [today's date]).

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