Is EGFR p.Pro1117Ser (c.3349C>T) pathogenic?

EGFR p.Pro1117Ser (c.3349C>T) is classified Uncertain significance in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-25). AlphaMissense: likely benign (0.0707); Very rare (popmax 0.00134%, afr); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Pro1117Ser (c.3349C>T)?

EGFR p.Pro1117Ser (c.3349C>T) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Pro1117Ser (c.3349C>T) in the general population?

EGFR p.Pro1117Ser (c.3349C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about EGFR p.Pro1117Ser (c.3349C>T)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

EGFR p.Pro1117Ser

c.3349C>T · rs777435609 · VCV1371112

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 0.71, phastCons 0.1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,238 bp · p 0.97 · regional, not allelic
Overall
CADD	11.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,624 alleles

Overall 6.21e-05% 1/1,611,494 alleles · very rare exomes 1/1,460,116 · genomes 0/151,378 · joint denominator

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.Pro1117Ser
Coding: c.3349C>T
MANE Select: NM_005228
dbSNP: rs777435609
Type: single nucleotide variant
Location: chr7:55205333 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 1117: the 'disordered' region

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 p.Pro1117Arg Uncertain significance ★★ ⚠ same residue
EGFR p.Pro1117= Likely benign ★★ same residue
EGFR p.Pro1117His Uncertain significance ★ ⚠ same residue
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

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-pro1117ser (accessed [today's date]).

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