Is EGFR p.Ile918= (c.2754C>T) pathogenic?

EGFR p.Ile918= (c.2754C>T) is classified Likely benign in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-13). Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ile918= (c.2754C>T)?

EGFR p.Ile918= (c.2754C>T) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Ile918= (c.2754C>T) in the general population?

EGFR p.Ile918= (c.2754C>T) is absent from gnomAD v4.1 (gnomAD).

EGFR p.Ile918=

c.2754C>T · rs1403940527 · VCV1606269

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -0.11, phastCons 0.03
Overall
CADD	8.073	PHRED · no single calibrated threshold — expert panels disagree

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: EGFR
Protein: p.Ile918=
Coding: c.2754C>T
MANE Select: NM_005228
dbSNP: rs1403940527
Type: single nucleotide variant
Location: chr7:55198769 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 918: the protein kinase domain

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

Disease context

Also linked: hereditary neoplastic syndrome

Similar variants

EGFR p.Ile918Met Uncertain significance ★ ⚠ same residue
EGFR c.1207+5G>A Uncertain significance ★★ same condition
EGFR c.1298+3A>G Uncertain significance ★★ same condition
EGFR c.1298+4A>G Uncertain significance ★★ same condition
EGFR c.1298+6T>C Uncertain significance ★★ same condition
EGFR c.1499-3C>T Uncertain significance ★★ same condition
EGFR c.1499-4G>T Uncertain significance ★★ same condition
EGFR c.1920-3C>T Uncertain significance ★★ same condition

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/egfr-p-ile918 (accessed [today's date]).

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