Is EGFR p.Pro136= (c.408C>T) pathogenic?

EGFR p.Pro136= (c.408C>T) is classified Likely benign in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Pro136= (c.408C>T)?

EGFR p.Pro136= (c.408C>T) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Pro136= (c.408C>T) in the general population?

EGFR p.Pro136= (c.408C>T) is absent from gnomAD v4.1 (gnomAD).

EGFR p.Pro136=

c.408C>T · VCV4733416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.103	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -0.15
Overall
CADD	8.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EGFR
Protein: p.Pro136=
Coding: c.408C>T
MANE Select: NM_005228
Type: single nucleotide variant
Location: chr7:55143472 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 136: a UniProt-annotated variant site (variant egfr viii; found in a lung cancer sample; somatic mutation; induces lung cancer when exogenously expressed)

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

Disease context

EGFR-related lung cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGFR c.1499-3C>T Uncertain significance ★★ same condition
EGFR c.2061+5G>A Uncertain significance ★★ same condition
EGFR c.2061+5G>T Uncertain significance ★★ same condition
EGFR c.2062-3C>G Uncertain significance ★★ same condition
EGFR c.3114+4T>G Uncertain significance ★★ same condition
EGFR c.3271+3G>A Uncertain significance ★★ same condition
EGFR c.629-3C>T Uncertain significance ★★ same condition
EGFR c.748-3T>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-pro136 (accessed [today's date]).

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