Is EGFR p.Phe254= (c.762C>T) pathogenic?

EGFR p.Phe254= (c.762C>T) is classified Likely benign in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-27). Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Phe254= (c.762C>T)?

EGFR p.Phe254= (c.762C>T) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Phe254= (c.762C>T) in the general population?

EGFR p.Phe254= (c.762C>T) is absent from gnomAD v4.1 (gnomAD).

EGFR p.Phe254=

c.762C>T · rs2128934856 · VCV1148751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 1.4	GERP 1.4, phastCons 1
Overall
CADD	8.996	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.Phe254=
Coding: c.762C>T
MANE Select: NM_005228
dbSNP: rs2128934856
Type: single nucleotide variant
Location: chr7:55154025 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 254: a β-strand; a UniProt-annotated variant site (variant egfr viii; found in a lung cancer sample; somatic mutation; induces lung cancer when exogenously expressed)

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

Disease context

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

Similar variants

EGFR p.Phe254Val Uncertain significance ★★ ⚠ same residue
EGFR p.Phe254Tyr Uncertain significance ★ ⚠ same residue
EGFR c.1499-3C>T Uncertain significance ★★ same condition
EGFR c.2061+5G>A Uncertain significance ★★ same condition
EGFR c.2061+5G>T Uncertain significance ★★ same condition
EGFR c.2062-3C>G Uncertain significance ★★ same condition
EGFR c.3114+4T>G Uncertain significance ★★ same condition
EGFR c.3271+3G>A 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-phe254 (accessed [today's date]).

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