Is EGFR p.Asp612= (c.1836C>T) pathogenic?

EGFR p.Asp612= (c.1836C>T) is classified Likely benign in EGFR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00549%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with EGFR p.Asp612= (c.1836C>T)?

EGFR p.Asp612= (c.1836C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is EGFR p.Asp612= (c.1836C>T) in the general population?

EGFR p.Asp612= (c.1836C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

EGFR p.Asp612=

c.1836C>T · rs150803480 · VCV1160876

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -6.7	GERP -5.5
Overall
CADD	0.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,086 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000743% 12/1,614,006 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0016%	62,468
African / African-American	0.00133%	74,912
European (non-Finnish)	0.000424%	236,005

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.Asp612=
Coding: c.1836C>T
MANE Select: NM_005228
dbSNP: rs150803480
Type: single nucleotide variant
Location: chr7:55165393 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 612: a disulfide bond

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.Asp612Gly Uncertain significance ★★ ⚠ same residue
EGFR p.Asp612Asn Uncertain significance ★ ⚠ same residue
EGFR p.Asp612Glu 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-asp612 (accessed [today's date]).

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