Is EGFR p.Pro20Gln (c.59C>A) pathogenic?

EGFR p.Pro20Gln (c.59C>A) is classified Conflicting classifications of pathogenicity in EGFR (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-07). AlphaMissense: likely benign (0.0937); Very rare (popmax 0.00554%, eas); Associated with lung carcinoma.

What condition is associated with EGFR p.Pro20Gln (c.59C>A)?

EGFR p.Pro20Gln (c.59C>A) is associated with lung carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Pro20Gln (c.59C>A) in the general population?

EGFR p.Pro20Gln (c.59C>A) is very rare (popmax 0.00554%, eas) (gnomAD).

What do computational predictors say about EGFR p.Pro20Gln (c.59C>A)?

AlphaMissense predicts likely benign (score 0.0937) — an in-silico prediction, not a clinical call.

EGFR p.Pro20Gln

c.59C>A · rs1028735720 · VCV802312

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0937 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00554%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lung carcinoma

Computational evidence

Protein change
AlphaMissense	0.0937	likely benign
REVEL	0.118	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.3
Regional constraint	o/e 1.72	unconstrained · MANE · 84 bp · p 9.2e-06 · regional, not allelic
Overall
CADD	0.262	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

Grpmax group 0.00554% East Asian · 2/36,090 alleles

Filtering AF 0.000918% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000343%

Overall 0.000263% 4/1,518,622 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00554%	18,045
European (non-Finnish)	0.000177%	564,417

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.Pro20Gln
Coding: c.59C>A
MANE Select: NM_005228
dbSNP: rs1028735720
Type: single nucleotide variant
Location: chr7:55019336 (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

lung carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

EGFR p.Pro20= Likely benign ★★ same residue
EGFR p.Pro20Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Pro20Leu 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
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-pro20gln (accessed [today's date]).

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