Is EGFR p.Ser925Phe (c.2774C>T) pathogenic?

EGFR p.Ser925Phe (c.2774C>T) is classified Uncertain significance in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: likely benign (0.1527); Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ser925Phe (c.2774C>T)?

EGFR p.Ser925Phe (c.2774C>T) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Ser925Phe (c.2774C>T) in the general population?

EGFR p.Ser925Phe (c.2774C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGFR p.Ser925Phe (c.2774C>T)?

AlphaMissense predicts likely benign (score 0.1527) — an in-silico prediction, not a clinical call.

EGFR p.Ser925Phe

c.2774C>T · rs2128968770 · VCV1510109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.1527	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -14.38	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -1.6, phastCons 0.38
Regional constraint	o/e 0.77	unconstrained · MANE · 29 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	26.3	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

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.Ser925Phe
Coding: c.2774C>T
MANE Select: NM_005228
dbSNP: rs2128968770
Type: single nucleotide variant
Location: chr7:55198789 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 925: an α-helix; the protein kinase domain

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.Ser925Thr Uncertain significance ★ ⚠ same residue
EGFR p.Ser925= Likely benign 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
EGFR c.3271+3G>A 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-ser925phe (accessed [today's date]).

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