Is EGFR p.Tyr74= (c.222T>C) pathogenic?

EGFR p.Tyr74= (c.222T>C) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-02). Rare (popmax 0.116%, eas); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Tyr74= (c.222T>C)?

EGFR p.Tyr74= (c.222T>C) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Tyr74= (c.222T>C) in the general population?

EGFR p.Tyr74= (c.222T>C) is rare (popmax 0.116%, eas) (gnomAD).

EGFR p.Tyr74=

c.222T>C · rs200383389 · VCV1167904

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

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 -3.2	GERP -4.7
Overall
CADD	1.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% East Asian · 52/44,888 alleles

Filtering AF 0.0907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0817%

Overall 0.00533% 86/1,614,190 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	863
South Asian	0.034%	2,938
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	8.47e-05%	1,180,032

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EGFR
Protein: p.Tyr74=
Coding: c.222T>C
MANE Select: NM_005228
dbSNP: rs200383389
Type: single nucleotide variant
Location: chr7:55142419 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 74: 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

Also linked: hereditary neoplastic syndrome

Similar variants

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
EGFR c.2061+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-tyr74 (accessed [today's date]).

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