Is EGFR p.Thr625Pro (c.1873A>C) pathogenic?

EGFR p.Thr625Pro (c.1873A>C) is classified Benign in EGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.1261); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with EGFR p.Thr625Pro (c.1873A>C)?

EGFR p.Thr625Pro (c.1873A>C) is associated with ovarian cancer (ClinVar).

How common is EGFR p.Thr625Pro (c.1873A>C) in the general population?

EGFR p.Thr625Pro (c.1873A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EGFR p.Thr625Pro (c.1873A>C)?

AlphaMissense predicts likely benign (score 0.1261) — an in-silico prediction, not a clinical call.

EGFR p.Thr625Pro

c.1873A>C · rs2128946528 · VCV2445283

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1261 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1261	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -9.64	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 4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.21	constrained · MANE · 5,789 bp · p 0.00013 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EGFR
Protein: p.Thr625Pro
Coding: c.1873A>C
MANE Select: NM_005228
dbSNP: rs2128946528
Type: single nucleotide variant
Location: chr7:55165430 (GRCh38)
Gene constraint: LOEUF 0.475 · pLI 0.98 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 76.29 · 393 PDB
Residue 625: a disulfide bond

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

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EGFR p.Thr625Ile Uncertain significance ★★ ⚠ same residue
EGFR p.Thr625= Likely benign ★★ same residue
EGFR p.Thr625Ser Uncertain significance ★ ⚠ same residue
EGFR p.Val592Ile Benign/Likely benign ★★ ⚠ same condition
EGFR p.Ile646Phe Likely pathogenic ★ ⚠ same condition
EGFR p.Ala21Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
EGFR p.Arg836Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
EGFR p.Asn1184Lys Conflicting classifications of pathogenicity ★ ⚠ 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-thr625pro (accessed [today's date]).

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