Is EGFR p.Ser720= (c.2160C>T) pathogenic?

EGFR p.Ser720= (c.2160C>T) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). Very rare (popmax 0.000932%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Ser720= (c.2160C>T)?

EGFR p.Ser720= (c.2160C>T) is associated with hereditary neoplastic syndrome, lung cancer (ClinVar).

How common is EGFR p.Ser720= (c.2160C>T) in the general population?

EGFR p.Ser720= (c.2160C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

EGFR p.Ser720=

c.2160C>T · rs1562784587 · VCV1107447

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.66 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.7	GERP -4.9
Overall
CADD	0.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,054 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000681% 11/1,614,120 alleles · very rare

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.Ser720=
Coding: c.2160C>T
MANE Select: NM_005228
dbSNP: rs1562784587
Type: single nucleotide variant
Location: chr7:55174019 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 720: a binding site; a β-strand; the protein kinase domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lung cancer

Similar variants

EGFR p.Ser720Cys Uncertain significance ★ ⚠ same residue
EGFR p.Ser720Phe 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
EGFR c.1499-4G>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-ser720 (accessed [today's date]).

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