Is EGFR p.Phe44Val (c.130T>G) pathogenic?

EGFR p.Phe44Val (c.130T>G) is classified Uncertain significance in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-20). AlphaMissense: likely benign (0.1027); Absent from gnomAD v4.1; Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Phe44Val (c.130T>G)?

EGFR p.Phe44Val (c.130T>G) is associated with EGFR-related lung cancer (ClinVar).

How common is EGFR p.Phe44Val (c.130T>G) in the general population?

EGFR p.Phe44Val (c.130T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGFR p.Phe44Val (c.130T>G)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

EGFR p.Phe44Val

c.130T>G · rs2128926193 · VCV1495199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -2.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2.4, phastCons 0.028
Regional constraint	o/e 0.75	unconstrained · MANE · 137 kb · p 6e-07 · regional, not allelic
Overall
CADD	15.66	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

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.Phe44Val
Coding: c.130T>G
MANE Select: NM_005228
dbSNP: rs2128926193
Type: single nucleotide variant
Location: chr7:55142327 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 44: an α-helix; 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 p.Phe44Ile Uncertain significance ★ ⚠ same residue
EGFR p.Phe44fs Pathogenic ★ same residue
EGFR p.Phe44Ser Uncertain significance ★★ ⚠ same residue
EGFR p.Phe44= 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

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-phe44val (accessed [today's date]).

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