Is EGFR p.Arg832Cys (c.2494C>T) pathogenic?

EGFR p.Arg832Cys (c.2494C>T) is classified Uncertain significance in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-30). AlphaMissense: ambiguous (0.368); Very rare (popmax 0.000424%, nfe); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Arg832Cys (c.2494C>T)?

EGFR p.Arg832Cys (c.2494C>T) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Arg832Cys (c.2494C>T) in the general population?

EGFR p.Arg832Cys (c.2494C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about EGFR p.Arg832Cys (c.2494C>T)?

AlphaMissense predicts ambiguous (score 0.368) — an in-silico prediction, not a clinical call.

EGFR p.Arg832Cys

c.2494C>T · rs745812480 · VCV936373

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.368 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.368	ambiguous
REVEL	0.489	indeterminate
SaProt	LLR -11.54	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 29 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,010 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,760 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.Arg832Cys
Coding: c.2494C>T
MANE Select: NM_005228
dbSNP: rs745812480
Type: single nucleotide variant
Location: chr7:55191743 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 832: the protein kinase domain

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.Arg832His Uncertain significance ★★ ⚠ same residue
EGFR p.Arg832= Likely benign ★★ same residue
EGFR p.Arg832Leu Uncertain significance ★ ⚠ 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

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-arg832cys (accessed [today's date]).

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