Is EGFR p.Ala10Glu (c.29C>A) pathogenic?

EGFR p.Ala10Glu (c.29C>A) is classified Uncertain significance in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-27). AlphaMissense: ambiguous (0.5145); Very rare (popmax 0.00144%, afr); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ala10Glu (c.29C>A)?

EGFR p.Ala10Glu (c.29C>A) is associated with EGFR-related lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Ala10Glu (c.29C>A) in the general population?

EGFR p.Ala10Glu (c.29C>A) is very rare (popmax 0.00144%, afr) (gnomAD).

What do computational predictors say about EGFR p.Ala10Glu (c.29C>A)?

AlphaMissense predicts ambiguous (score 0.5145) — an in-silico prediction, not a clinical call.

EGFR p.Ala10Glu

c.29C>A · rs1217714114 · VCV1441042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5145 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, afr)

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.5145	ambiguous
REVEL	0.505	indeterminate
SaProt	LLR -11.03	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP 1.2, phastCons 0.11
Regional constraint	o/e 1.72	unconstrained · MANE · 84 bp · p 9.2e-06 · regional, not allelic
Overall
CADD	13.74	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 0.00144% African / African-American · 1/69,466 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000264% 4/1,516,690 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00144%	69,466
European (non-Finnish)	0.000266%	376,054

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.Ala10Glu
Coding: c.29C>A
MANE Select: NM_005228
dbSNP: rs1217714114
Type: single nucleotide variant
Location: chr7:55019306 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB

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.Ala10= Likely benign ★★ same residue
EGFR p.Ala10Gly Uncertain significance ★ ⚠ same residue
EGFR p.Ala10Thr Uncertain significance ★ ⚠ same residue
EGFR p.Ala10Val 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

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-ala10glu (accessed [today's date]).

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