Is EGFR p.Val550= (c.1650G>A) pathogenic?

EGFR p.Val550= (c.1650G>A) is classified Conflicting classifications of pathogenicity in EGFR (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-27). Very rare (popmax 0.00133%, afr); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Val550= (c.1650G>A)?

EGFR p.Val550= (c.1650G>A) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Val550= (c.1650G>A) in the general population?

EGFR p.Val550= (c.1650G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

EGFR p.Val550=

c.1650G>A · rs1261257677 · VCV1126767

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss, 18 bp away · masked 0 · deltas
Pangolin	Δ0.24	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.8	GERP 1, phastCons 1
Overall
CADD	5.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,924 alleles

Overall 0.000657% 1/152,208 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.Val550=
Coding: c.1650G>A
MANE Select: NM_005228
dbSNP: rs1261257677
Type: single nucleotide variant
Location: chr7:55163751 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 550: a β-strand; a disulfide bond

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.Val550Leu Uncertain significance ★ ⚠ same residue
EGFR p.Val550Met 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
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-val550 (accessed [today's date]).

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