Is EGFR p.Asp994= (c.2982C>T) pathogenic?

EGFR p.Asp994= (c.2982C>T) is classified Benign/Likely benign in EGFR (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 30.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with lung cancer.

What condition is associated with EGFR p.Asp994= (c.2982C>T)?

EGFR p.Asp994= (c.2982C>T) is associated with lung cancer, hereditary neoplastic syndrome (ClinVar).

EGFR p.Asp994=

Q: How common is EGFR p.Asp994= (c.2982C>T) in the general population?

EGFR p.Asp994= (c.2982C>T) is common (popmax 30.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2982C>T · rs2293347 · VCV259679

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 30.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

lung cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.11 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.93, phastCons 1
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.7% East Asian · 13,771/44,852 alleles

Filtering AF 30.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.1%

Overall 11.6% 187,260/1,614,064 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	30.7%	3
South Asian	22.5%	4
Finnishnot grpmax-eligible	19.3%	5
Admixed American	14.5%	7
Remaining individualsnot grpmax-eligible	11.8%	8
Amishnot grpmax-eligible	10.3%	10
European (non-Finnish)	10.2%	10
Ashkenazi Jewishnot grpmax-eligible	7.4%	14
Middle Eastern	7.29%	14
African / African-American	2.45%	41

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.Asp994=
Coding: c.2982C>T
MANE Select: NM_005228
dbSNP: rs2293347
Type: single nucleotide variant
Location: chr7:55201223 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 994: a turn

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

Disease context

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

Also linked: hereditary neoplastic syndrome

Similar variants

EGFR p.Asp994Asn Uncertain significance ★★ ⚠ same residue
EGFR p.Asp994Ala 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
EGFR c.1499-4G>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-asp994 (accessed [today's date]).

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