Is EGFR p.Pro848= (c.2544G>A) pathogenic?

EGFR p.Pro848= (c.2544G>A) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.03%, amr); Associated with lung cancer.

What condition is associated with EGFR p.Pro848= (c.2544G>A)?

EGFR p.Pro848= (c.2544G>A) is associated with lung cancer, endometrial carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Pro848= (c.2544G>A) in the general population?

EGFR p.Pro848= (c.2544G>A) is ultra-rare (popmax 0.03%, amr) (gnomAD).

EGFR p.Pro848=

c.2544G>A · rs104886012 · VCV132949

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

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 -11	GERP -3.8
Overall
CADD	0.309	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.03% Admixed American · 18/60,020 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.0039% 63/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0112%	8,929
European (non-Finnish)	0.00305%	32,779
African / African-American	0.00267%	37,509

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.Pro848=
Coding: c.2544G>A
MANE Select: NM_005228
dbSNP: rs104886012
Type: single nucleotide variant
Location: chr7:55191793 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 848: the protein kinase domain

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

Also linked: endometrial carcinoma hereditary neoplastic syndrome

Similar variants

EGFR p.Pro848Ser Uncertain significance ★★ ⚠ same residue
EGFR p.Pro848Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Pro848Gln Uncertain significance ★ ⚠ 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
EGFR c.1499-3C>T 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-pro848 (accessed [today's date]).

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