Is EGFR p.Leu760= (c.2280C>G) pathogenic?

EGFR p.Leu760= (c.2280C>G) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-14). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Leu760= (c.2280C>G)?

EGFR p.Leu760= (c.2280C>G) is associated with hereditary neoplastic syndrome, lung cancer (ClinVar).

How common is EGFR p.Leu760= (c.2280C>G) in the general population?

EGFR p.Leu760= (c.2280C>G) is absent from gnomAD v4.1 (gnomAD).

EGFR p.Leu760=

c.2280C>G · rs397517103 · VCV2840077

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 -5.5	GERP -5
Overall
CADD	0.629	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.Leu760=
Coding: c.2280C>G
MANE Select: NM_005228
dbSNP: rs397517103
Type: single nucleotide variant
Location: chr7:55174817 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 760: an α-helix; the protein kinase domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lung cancer

Similar variants

EGFR p.Leu760Pro Uncertain significance ★ ⚠ same residue
EGFR p.Leu760Phe 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

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-leu760 (accessed [today's date]).

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