Is EGFR p.Gln71Pro (c.212A>C) pathogenic?

EGFR p.Gln71Pro (c.212A>C) is classified Uncertain significance in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-15). AlphaMissense: likely benign (0.1239); Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Gln71Pro (c.212A>C)?

EGFR p.Gln71Pro (c.212A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Gln71Pro (c.212A>C) in the general population?

EGFR p.Gln71Pro (c.212A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about EGFR p.Gln71Pro (c.212A>C)?

AlphaMissense predicts likely benign (score 0.1239) — an in-silico prediction, not a clinical call.

EGFR p.Gln71Pro

c.212A>C · VCV3715775

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1239 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1239	likely benign
REVEL	0.457	indeterminate
SaProt	LLR -4.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 137 kb · p 6e-07 · regional, not allelic
Overall
CADD	20.2	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

Grpmax group 0.00133% African / African-American · 1/75,062 alleles

Overall 6.84e-05% 1/1,461,868 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.Gln71Pro
Coding: c.212A>C
MANE Select: NM_005228
Type: single nucleotide variant
Location: chr7:55142409 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 71: 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

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

Similar variants

EGFR p.Gln71= Likely benign ★★ same residue
EGFR p.Gln71Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Gln71Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
EGFR p.Gln71His 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-gln71pro (accessed [today's date]).

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