Is EGFR p.Ala1201= (c.3603G>A) pathogenic?

EGFR p.Ala1201= (c.3603G>A) is classified Likely benign in EGFR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). Ultra-rare (popmax 0.0274%, sas); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ala1201= (c.3603G>A)?

EGFR p.Ala1201= (c.3603G>A) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Ala1201= (c.3603G>A) in the general population?

EGFR p.Ala1201= (c.3603G>A) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

EGFR p.Ala1201=

c.3603G>A · rs202156403 · VCV1143996

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

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 -3.1
Overall
CADD	0.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,076 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.0028% 41/1,461,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
Remaining individualsnot grpmax-eligible	0.0064%	15,627
Finnishnot grpmax-eligible	0.00625%	16,008
Admixed American	0.00167%	60,008
African / African-American	0.00133%	74,994
European (non-Finnish)	0.000508%	196,669

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.Ala1201=
Coding: c.3603G>A
MANE Select: NM_005228
dbSNP: rs202156403
Type: single nucleotide variant
Location: chr7:55205587 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB

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

Disease context

Also linked: hereditary neoplastic syndrome

Similar variants

EGFR p.Ala1201Glu Uncertain significance ★★ ⚠ same residue
EGFR p.Ala1201Val Uncertain significance ★★ ⚠ same residue
EGFR p.Ala1201Ser Uncertain significance ★ ⚠ same residue
EGFR p.Ala1201Thr Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala1201 (accessed [today's date]).

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