Is EGFR p.Ile673Phe (c.2017A>T) pathogenic?

EGFR p.Ile673Phe (c.2017A>T) is classified Uncertain significance in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-16). AlphaMissense: ambiguous (0.4756); Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ile673Phe (c.2017A>T)?

EGFR p.Ile673Phe (c.2017A>T) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Ile673Phe (c.2017A>T) in the general population?

EGFR p.Ile673Phe (c.2017A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGFR p.Ile673Phe (c.2017A>T)?

AlphaMissense predicts ambiguous (score 0.4756) — an in-silico prediction, not a clinical call.

EGFR p.Ile673Phe

c.2017A>T · rs1199980775 · VCV1395785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4756 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.4756	ambiguous
REVEL	0.612	indeterminate
SaProt	LLR -8.91	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 29 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ile673Phe
Coding: c.2017A>T
MANE Select: NM_005228
dbSNP: rs1199980775
Type: single nucleotide variant
Location: chr7:55173080 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 673: a β-strand

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.Ile673Met Uncertain significance ★ ⚠ same residue
EGFR p.Ile673Val Uncertain significance ★★ ⚠ same residue
EGFR p.Ile673= Likely benign ★★ 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

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-ile673phe (accessed [today's date]).

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