Is EGFR p.Lys757= (c.2271G>A) pathogenic?

EGFR p.Lys757= (c.2271G>A) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-16). Absent from gnomAD v4.1; Associated with lung cancer.

What condition is associated with EGFR p.Lys757= (c.2271G>A)?

EGFR p.Lys757= (c.2271G>A) is associated with lung cancer (ClinVar).

How common is EGFR p.Lys757= (c.2271G>A) in the general population?

EGFR p.Lys757= (c.2271G>A) is absent from gnomAD v4.1 (gnomAD).

EGFR p.Lys757=

c.2271G>A · rs1786526710 · VCV2827378

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 1.8	GERP -1.7, phastCons 1
Overall
CADD	8.32	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.Lys757=
Coding: c.2271G>A
MANE Select: NM_005228
dbSNP: rs1786526710
Type: single nucleotide variant
Location: chr7:55174808 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 757: a UniProt-annotated variant site (found in a lung cancer sample); an α-helix; the protein kinase domain; a cross-link site

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

Disease context

lung cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGFR p.Lys757Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Lys757Asn Uncertain significance ★ ⚠ same residue
EGFR p.Lys757Met Uncertain significance ★ ⚠ same residue
EGFR p.Arg1031Gln Uncertain significance ★★ ⚠ same condition
EGFR p.Arg165Trp Uncertain significance ★★ ⚠ same condition
EGFR p.Arg671His Uncertain significance ★★ ⚠ same condition
EGFR p.Arg831Cys Uncertain significance ★★ ⚠ same condition
EGFR p.Arg999His 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-lys757 (accessed [today's date]).

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