Is EGFR p.Ser511Tyr (c.1532C>A) pathogenic?

EGFR p.Ser511Tyr (c.1532C>A) is classified Conflicting classifications of pathogenicity in EGFR (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-08-17). AlphaMissense: ambiguous (0.5334); Ultra-rare (popmax 0.0199%, nfe); Associated with EGFR-related lung cancer.

What condition is associated with EGFR p.Ser511Tyr (c.1532C>A)?

EGFR p.Ser511Tyr (c.1532C>A) is associated with EGFR-related lung cancer, lung cancer, hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Ser511Tyr (c.1532C>A) in the general population?

EGFR p.Ser511Tyr (c.1532C>A) is ultra-rare (popmax 0.0199%, nfe) (gnomAD).

What do computational predictors say about EGFR p.Ser511Tyr (c.1532C>A)?

AlphaMissense predicts ambiguous (score 0.5334) — an in-silico prediction, not a clinical call.

EGFR p.Ser511Tyr

c.1532C>A · rs371114444 · VCV854259

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.5334 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0199%, nfe)

Conditions

EGFR-related lung cancer

Computational evidence

Protein change
AlphaMissense	0.5334	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -13.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 8,628 bp · p 0.0087 · regional, not allelic
Overall
CADD	24.7	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 0.0199% European (non-Finnish) · 235/1,180,044 alleles

Filtering AF 0.0178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.0155% 250/1,614,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0199%	5,021
Remaining individualsnot grpmax-eligible	0.016%	6,251
Finnishnot grpmax-eligible	0.00469%	21,334
Admixed American	0.00167%	60,034
African / African-American	0.00133%	75,066

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.Ser511Tyr
Coding: c.1532C>A
MANE Select: NM_005228
dbSNP: rs371114444
Type: single nucleotide variant
Location: chr7:55161532 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 511: a disulfide bond

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

Disease context

Also linked: lung cancer hereditary neoplastic syndrome

Similar variants

EGFR p.Ser511Phe 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
EGFR c.1920-3C>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-ser511tyr (accessed [today's date]).

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