Is EGFR p.Ala1118= (c.3354G>A) pathogenic?

EGFR p.Ala1118= (c.3354G>A) is classified Likely benign in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0201%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Ala1118= (c.3354G>A)?

EGFR p.Ala1118= (c.3354G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Ala1118= (c.3354G>A) in the general population?

EGFR p.Ala1118= (c.3354G>A) is ultra-rare (popmax 0.0201%, afr) (gnomAD).

EGFR p.Ala1118=

c.3354G>A · rs199838215 · VCV1108349

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, afr)

Conditions

hereditary neoplastic syndrome

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
Constraint at this position
Conservation	phyloP -2.4	GERP -3.4
Overall
CADD	0.896	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% African / African-American · 15/74,618 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00993%

Overall 0.00639% 103/1,611,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0201%	4,975
Finnishnot grpmax-eligible	0.0125%	7,994
Remaining individualsnot grpmax-eligible	0.00961%	10,405
East Asian	0.00893%	11,204
European (non-Finnish)	0.00585%	17,084
South Asian	0.0011%	90,806

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.Ala1118=
Coding: c.3354G>A
MANE Select: NM_005228
dbSNP: rs199838215
Type: single nucleotide variant
Location: chr7:55205338 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 1118: the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGFR p.Ala1118Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Ala1118Val Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Ala1118Ser 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-ala1118 (accessed [today's date]).

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