Is EGFR c.628+252C>G pathogenic?

EGFR c.628+252C>G is classified Benign in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-10). Common (popmax 55.4%, sas) — too common for a highly-penetrant pathogenic allele.

EGFR c.628+252C>G

Q: How common is EGFR c.628+252C>G in the general population?

EGFR c.628+252C>G is common (popmax 55.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs2075111 · VCV1288886

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 55.4%, sas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +252	deep intronic (+252 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.005	GERP -0.55
Overall
CADD	0.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.4% South Asian · 2,673/4,822 alleles

Filtering AF 53.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 53%

Overall 50.9% 77,430/152,048 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	55.4%	2
Ashkenazi Jewishnot grpmax-eligible	55.3%	2
European (non-Finnish)	52.3%	2
Amishnot grpmax-eligible	51.8%	2
African / African-American	50.9%	2
Remaining individualsnot grpmax-eligible	50.7%	2
Admixed American	49.6%	2
Finnishnot grpmax-eligible	48.2%	2
Middle Eastern	46.9%	2
East Asian	35.2%	3

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
Coding: c.628+252C>G
MANE Select: NM_005228
dbSNP: rs2075111
Type: single nucleotide variant
Location: chr7:55151614 (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

Similar variants

EGFR p.Gly428Asp Pathogenic ★★ same type
EGFR c.1207+5G>A Uncertain significance ★★ same type
EGFR c.1298+3A>G Uncertain significance ★★ same type
EGFR c.1298+4A>G Uncertain significance ★★ same type
EGFR c.1298+6T>C Uncertain significance ★★ same type
EGFR c.1499-3C>T Uncertain significance ★★ same type
EGFR c.1499-4G>T Uncertain significance ★★ same type
EGFR c.1920-3C>T Uncertain significance ★★ same type

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-c-628-plus-252c-g (accessed [today's date]).

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